RESUMO
BACKGROUND: According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. OBJECTIVE: To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. METHODS: We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. RESULTS: The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. CONCLUSION: 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.
Assuntos
Antagonistas de Androgênios , Ácidos Carboxílicos , Ciclobutanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Ácidos Carboxílicos/uso terapêutico , Ciclobutanos/uso terapêutico , Masculino , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Idoso , Pessoa de Meia-Idade , Antagonistas de Androgênios/uso terapêutico , Padrão de Cuidado , United States Department of Veterans Affairs , Estados Unidos , Guias de Prática Clínica como Assunto , Idoso de 80 Anos ou mais , RecidivaRESUMO
INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. Currently, more than 100 million cases of COVID-19 have been confirmed worldwide, with over 2.4 million mortalities. The pandemic affects people of all ages but older individuals and those with severe chronic illnesses, including cancer patients, are at higher risk. PATIENT CONCERNS: The impact of cancer treatment on the progression of COVID-19 is unclear. Therefore, we assessed the effects of chemotherapy on COVID-19 outcomes for 2 cancer patients. On January 24, 2020, a level I response to a major public health emergency was initiated in Hubei Province, China, which includes Enshi Autonomous Prefecture that has a population of 4.026 million people. As of April 30, 2020, 252 confirmed cases of COVID-19 and 11 asymptomatic carriers were identified in Enshi. DIAGNOSIS: Among the confirmed cases and asymptomatic carriers, 2 patients were identified who were previously diagnosed with malignant tumors, including one with hepatocellular carcinoma and the other with cardia carcinoma. INTERVENTIONS: These 2 patients were receiving or just completed chemotherapy at the time of their COVID-19 diagnosis. OUTCOMES: Both patients were followed and presented favorable outcomes. The positive outcomes for these 2 patients could be partially explained by their recent chemotherapy that impacted their immune status. Also, their relatively younger ages and lack of comorbidities were likely factors in their successful recovery from COVID-19. CONCLUSIONS: Anticancer treatment might enhance a patient's ability to respond favorably to COVID-19 infection. However, anticancer treatment is likely to impact immune function differently in different individuals, which can influence disease outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , COVID-19/imunologia , Neoplasias Hepáticas/tratamento farmacológico , SARS-CoV-2/imunologia , Neoplasias Gástricas/tratamento farmacológico , Adulto , COVID-19/complicações , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Ciclobutanos/uso terapêutico , Docetaxel/uso terapêutico , Quimioterapia Combinada/métodos , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/imunologia , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , RNA Viral/isolamento & purificação , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sorafenibe/uso terapêutico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/imunologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.
Assuntos
Ciclobutanos/toxicidade , Ciclobutanos/uso terapêutico , Obesidade/tratamento farmacológico , Fenômenos Reprodutivos Fisiológicos/efeitos dos fármacos , Rosuvastatina Cálcica/toxicidade , Rosuvastatina Cálcica/uso terapêutico , Testículo/efeitos dos fármacos , Adulto , Animais , Humanos , Masculino , Modelos Animais , Ratos , Ratos WistarRESUMO
BACKGROUND: Compared with single-drug TACE, our previous phase III study demonstrated that triple-drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single-drug TACE. METHODS: Patients in the triple-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center. RESULTS: No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple-drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single-drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple-drug chemotherapy benefit versus single-drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller). CONCLUSIONS: Triple-drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single-drug TACE.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Ciclobutanos/administração & dosagem , Epirubicina/administração & dosagem , Neoplasias Hepáticas/terapia , Mitomicina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Ciclobutanos/uso terapêutico , Emulsões , Epirubicina/uso terapêutico , Óleo Etiodado/administração & dosagem , Óleo Etiodado/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
We introduce a novel strategy to enhance the fluorescence brightness of organic-molecule-based nanoparticles in the second near-infrared window (NIR-II, 1000-1700 nm) by fabricating J-aggregate nanoparticles SQP-NPs(J). Our prepared J-aggregate nanoparticles SQP-NPs(J) show an emission maximum near 1100 nm, and the emission intensity is 4.8-fold higher than that of H-aggregate SQP-NPs(H). In addition, SQP-NPs(J) can be used for NIR-II imaging guided photothermal therapy on MCF-7 tumor-bearing mice due to the fact that SQP-NPs(J) have highly effective photothermal properties, which are significant for precise tumor diagnostics and treatments.
Assuntos
Ciclobutanos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanopartículas/química , Fenóis/uso terapêutico , Fototerapia , Animais , Ciclobutanos/síntese química , Ciclobutanos/química , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Raios Infravermelhos , Injeções Intravenosas , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Fenóis/síntese química , Fenóis/químicaRESUMO
Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. Our efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, we discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by X-ray crystallographic analysis. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clinical candidate for the treatment of JAK1-mediated autoimmune diseases.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Ciclobutanos/farmacologia , Janus Quinase 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Sulfonamidas/farmacologia , Animais , Artrite Experimental/tratamento farmacológico , Ciclobutanos/química , Ciclobutanos/farmacocinética , Ciclobutanos/uso terapêutico , Cães , Avaliação Pré-Clínica de Medicamentos , Humanos , Concentração Inibidora 50 , Janus Quinase 1/química , Janus Quinase 2/antagonistas & inibidores , Modelos Moleculares , Conformação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/química , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Pirróis/química , Pirróis/farmacocinética , Pirróis/uso terapêutico , Ratos , Especificidade por Substrato , Sulfonamidas/química , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapêutico , Distribuição TecidualRESUMO
To evaluate the safety and efficacy of transarterial arterial chemoembolization (TACE) with gelatin sponge particles (GSPs-TACE) and Huaier granule to treat primary hepatic carcinoma (PHC).A series of 62 patients with PHC were included between June 2009 and December 2011, and randomly assigned to a control (nâ=â31) or an experimental group (nâ=â31). The control patients received TACE with 350 to 560âµm GSPs plus lobaplatin chemotherapy. Patients in the experimental group received TACE plus Huaier granule. Treatment safety and mid-to-long-term efficacy were evaluated.Follow-up ranged from 12 to 24 months with a mean of 28.7 months. The 6- and 12-month overall survivals were 100% and 93.5% in the experimental group and 90.3% and 80.6% in control group, respectively. The difference in overall survival at 12 months was significant (χâ=â5.213, Pâ<â.05), but the difference in median survival in the experimental group (20.6 months) and control group (17.1 months) patients was not significant (χâ=â0.745, Pâ>â.05). The number of TACE procedures in the experimental group (2.9â±â8.7) and control group (4.1â±â7.3) patients was significantly different (χâ=â7.262, Pâ<â.05). The 6-month (87.1% vs. 73.3%, χâ=â5.945) and 12-month (72.4% vs. 64.3%, χâ=â6.384) tumor objective response rates in the experimental and control groups were significantly different (Pâ<â.05). There were no statistically significant differences in the occurrence of treatment-related adverse reactions in the 2 groups.Transarterial chemoembolization with GSPs and Huaier granule was safe and effective for treating PHC patients.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Misturas Complexas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada/efeitos adversos , Ciclobutanos/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Compostos Organoplatínicos/uso terapêutico , Fatores de Tempo , Trametes , Resultado do TratamentoRESUMO
BACKGROUND: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00454519.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Gastrointestinais/patologia , Neoplasias dos Genitais Femininos/patologia , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/mortalidade , Carcinoma/secundário , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/instrumentação , Quimioterapia do Câncer por Perfusão Regional/métodos , Ciclobutanos/administração & dosagem , Ciclobutanos/farmacologia , Ciclobutanos/uso terapêutico , Docetaxel , Sinergismo Farmacológico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/farmacologia , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
UNLABELLED: Objecive: To investigate the clinical safety and efficacy of CT-guided 125iodine (125I) seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol in treating patients with advanced lung cancer. MATERIALS AND METHODS: Patients with advanced lung cancer and treated with spiral CT-guided 125I seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol were recruited. RESULTS: Of the 36 patients, there were 40 nidi in total. The contrast-enhanced CT evaluation was conducted 60 d after treatment. Response evaluation suggested that 4 patients achieved complete remission (CR), 24 partial remission (PR), 4 stable disease (SD) and 4 progression disease (PD), with a total response rate of 77.8% (28/36). CONCLUSIONS: CT-guided 125I seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol are safe and effective in treating patients with advanced lung cancer.
Assuntos
Braquiterapia , Quimiorradioterapia , Ciclobutanos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/terapia , Inoculação de Neoplasia , Compostos Organoplatínicos/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/terapia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Óleo Etiodado/uso terapêutico , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Radioterapia Guiada por Imagem , Indução de Remissão , Carcinoma de Pequenas Células do Pulmão/patologia , Tomografia Computadorizada por Raios XRESUMO
Extensive efforts have been devoted to the development of near-infrared (NIR) dye-based imaging probes and/or photothermal agents for cancer theranostics in vivo. However, the intrinsic chemical instability and self-aggregation properties of NIR dyes in physiological condition limit their widely applications in the pre-clinic study in living animals. Squaraine dyes are among the most promising NIR fluorophores with high absorption coefficiencies, bright fluorescence and photostability. By introducing dicyanovinyl groups into conventional squaraine (SQ) skeleton. These acceptor-substituted SQ dyes not only show superior NIR fluorescence properties (longer wavelength, higher quantum yield) but also exhibit more chemical robustness. In this work, we demonstrated highly stable and biocompatible supramolecular adducts of SQ and the natural carrier protein, i.e., bovine serum albumin (BSA) (SQâBSA) for tumor targeted imaging and photothermal therapy in vivo. SQ was selectively bound to BSA hydrophobic domain via hydrophobic and hydrogen bonding interactions with up to 80-fold enhanced fluorescence intensity. By covalently conjugating target ligands to BSA, the SQâBSA was capable of targeting tumor sites and allowed for monitoring the time-dependent biodistribution of SQâBSA, which consequently determined the protocol of photothermal therapy in vivo. We envision that this supramolecular strategy for selectively binding functional imaging agents and/or drugs into human serum albumin might potentially utilize in the preclinical and even clinic studies in the future.
Assuntos
Ciclobutanos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/terapia , Fenóis/uso terapêutico , Animais , Bovinos , Linhagem Celular Tumoral , Ciclobutanos/química , Feminino , Corantes Fluorescentes/química , Humanos , Hipertermia Induzida , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Simulação de Acoplamento Molecular , Imagem Óptica , Fenóis/química , Fototerapia , Soroalbumina Bovina/química , Soroalbumina Bovina/uso terapêuticoRESUMO
Treatment of alopecia areata is dependent on age of patient as well as the extent and duration of scalp involvement. Treatments include steroids, topical immunotherapy, topical minoxidil, anthralin, and immunosuppressants. Each case must be dealt with on a customized individual basis.
Assuntos
Corticosteroides/administração & dosagem , Alopecia em Áreas/tratamento farmacológico , Administração Cutânea , Antralina/uso terapêutico , Ciclobutanos/uso terapêutico , Ciclopropanos/uso terapêutico , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Injeções Intralesionais , Metotrexato/uso terapêutico , Minoxidil/uso terapêutico , Terapia PUVA , Grupos de AutoajudaRESUMO
Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/economia , Fármacos Antiobesidade/farmacologia , Apetite/fisiologia , Terapia Combinada , Comorbidade , Análise Custo-Benefício , Ciclobutanos/uso terapêutico , Diabetes Mellitus Tipo 2/epidemiologia , Dieta para Diabéticos , Combinação de Medicamentos , Terapia por Exercício , Frutose/administração & dosagem , Frutose/análogos & derivados , Frutose/uso terapêutico , Hormônios Gastrointestinais/metabolismo , Humanos , Incretinas/fisiologia , Insulina/metabolismo , Secreção de Insulina , Intestinos/efeitos dos fármacos , Lactonas/uso terapêutico , Leptina/fisiologia , Estilo de Vida , Modelos Biológicos , Neuropeptídeos/fisiologia , Obesidade/dietoterapia , Obesidade/economia , Obesidade/epidemiologia , Obesidade/terapia , Orlistate , Fentermina/administração & dosagem , Fentermina/uso terapêutico , Fitoterapia , Piperidinas/uso terapêutico , Preparações de Plantas/uso terapêutico , Pirazóis/uso terapêutico , Rimonabanto , TopiramatoRESUMO
PURPOSE: The prevalence of obesity has been increasing in the United States. We set out to investigate the use of pharmacologic and non-pharmacologic therapy for the treatment of obesity in recent years. METHODS: We included 2630 men and 2702 women who took part in the National Health and Nutrition Examination Survey from 2007 to 2008. We analyzed their demographic and anthropometric data and their weight and drug history. RESULTS: A total of 45.9% of men and 45.0% of women were candidates for treatment (body mass index ≥30 kg/m(2), or ≥27 kg/m(2) with risk factors). Among these participants, 85.1% considered themselves overweight, 90.1% would like to lose weight, 61.9% had dietary changes, 36.5% exercised, 3.7% took nonprescription drugs, and 2.2% took prescription drugs to control weight during the preceding year. During the preceding month, 0.5% and 0.1% of participants were taking phentermine and orlistat, respectively. There were no participants on sibutramine. CONCLUSIONS: Although obesity is highly prevalent, only a small percentage of obese Americans are on anti-obesity medication. The withdrawal of sibutramine would have minimal impact on the general population. There is a need for more lifestyle changes in the majority of obese individuals.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Exercício Físico , Obesidade/epidemiologia , Obesidade/terapia , Adulto , Ciclobutanos/uso terapêutico , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Estados Unidos/epidemiologia , Redução de PesoRESUMO
BACKGROUND: Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES: Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS: A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS: Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS: The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION: The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Ciclobutanos/uso terapêutico , Lactonas/uso terapêutico , Obesidade/tratamento farmacológico , Piperidinas/uso terapêutico , Pirazóis/uso terapêutico , Fármacos Antiobesidade/economia , Análise Custo-Benefício , Ciclobutanos/economia , Custos de Medicamentos/estatística & dados numéricos , Exercício Físico , Feminino , Humanos , Lactonas/economia , Masculino , Pessoa de Meia-Idade , Orlistate , Piperidinas/economia , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/métodos , Pirazóis/economia , Rimonabanto , Comportamento de Redução do Risco , Resultado do TratamentoRESUMO
In this study, we investigated the effects of a Chinese herbal medicine formula xiao-gao-jiang-zhuo (XGJZ) in obese rats induced by a high-fat diet. Ten male rats in the normal group were fed with a standard diet. Another 50 male obese rats were induced by a 12-week high-fat diet feeding, and were randomly divided into five groups (n = 10 per group): the model group, the high-dose XGJZ group, the middle-dose XGJZ group, the low-dose XGJZ group, and the sibutramine group. After 14 weeks of treatment, body weight, abdominal fat, blood lipid and serum insulin level were measured, and the protein and gene expression of PTP1B in liver tissue was tested. Our data showed that the body weight of the high-dose and middle-dose groups and the sibutramine group had significant differences in comparison with the model group (p < 0.05), and all three dose groups had significantly reduced abdominal fat (p < 0.05). The triglyceride level of the three dose groups and the sibutramine group, and the total cholesterol level of the middle-dose group were all significantly reduced (p < 0.05). The serum insulin of the high-dose and middle-dose groups also decreased significantly (p < 0.05). The expression of hepatic PTP1B mRNA of the three dose groups decreased significantly in comparison with the model group (p < 0.05 or 0.01). The expression of hepatic PTP1B protein of the high-dose and middle-dose groups decreased significantly (p < 0.05). Our data suggested that XGJZ can modulate the body weight, abdominal fat and blood lipid in the obese rats, and this modulation might improve insulin resistance by inhibiting the PTP1B signal pathway.
Assuntos
Fármacos Antiobesidade/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Fitoterapia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Gordura Abdominal/metabolismo , Animais , Fármacos Antiobesidade/uso terapêutico , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Ciclobutanos/farmacologia , Ciclobutanos/uso terapêutico , Gorduras na Dieta/efeitos adversos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Expressão Gênica , Insulina/sangue , Resistência à Insulina , Fígado/metabolismo , Masculino , Obesidade/induzido quimicamente , Obesidade/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangueRESUMO
OBJECTIVE: To observe clinical effect differences between electric-heat needle combined with acupoint sticking therapy and oral administration of western medicine for treatment of simple obesity of spleen deficiency and dampness stagnation type. METHODS: The electric-heat needle combined with acupoint sticking therapy group (n=80) was treated with acupuncture at Daimai (GB 26), Zhongwan (CV 12), Zusanli (ST 36), etc. and acupoint sticking therapy at Shenque (CV 8), Zhongwan (CV 12), Guanyuan (CV 4), etc., and the western medicine group (n=41) was treated with oral administration of Sibutramine Hydrochloride capsules. The therapeutic effects were observed after 4 weeks of treatment in the two groups. RESULTS: The total effective rate was 97.5% (78/80) in the electric-heat needle combined with acupoint sticking therapy group and 70.7% (29/41) in the western medicine group, with a significant difference between the two groups (P < 0.05). CONCLUSION: Electric-heat needle combined with acupoint stic-king therapy has better therapeutic effect on simple obesity of spleen deficiency and dampness stagnation type than that of oral administration of Sibutramine Hydrochloride capsules.
Assuntos
Terapia por Acupuntura , Obesidade/terapia , Pontos de Acupuntura , Adulto , Ciclobutanos/uso terapêutico , Eletroacupuntura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/fisiopatologia , Baço/fisiopatologia , Resultado do TratamentoAssuntos
Alopecia em Áreas/terapia , Cabelo/crescimento & desenvolvimento , Imunoterapia , Psoríase/terapia , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Alopecia em Áreas/complicações , Alopecia em Áreas/patologia , Calcitriol/análogos & derivados , Calcitriol/uso terapêutico , Ciclobutanos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Psoríase/complicações , Psoríase/patologiaRESUMO
5-HT and noradrenaline are important neurotransmitters that control increase in body mass and are involved in the pathophysiology of obesity and depression. Sibutramine, an established anti-obesity agent, and duloxetine, an anti-depressant agent, are serotonin noradrenaline reuptake inhibitors (SNRIs). The objective of the present study was to compare the anti-obesity effect of duloxetine with sibutramine along with its effect on blood pressure and depression in obese rats. The secondary objective of the study was to determine if a relationship exists between obesity and depression. Obesity was induced by high-fat diet (HFD) in healthy male Sprague-Dawley rats. After 5 weeks of feeding HFD, animals were overweight (17.57%) with high food intake (57.15%) in comparison with normal animals. These obese animals were treated with duloxetine (30 mg x kg(-1), p.o.) and sibutramine (5 mg x kg(-1), p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg x kg(-1), p.o.). Our results depict that duloxetine was as effective as sibutramine in reducing food intake, body mass, and relative adiposity, and increasing rectal temperature with an added advantage of decreasing blood pressure, which sibutramine failed to do. Besides reduction in body mass, unlike sibutramine, duloxetine improved depressive state as evaluated by despair swimming test, tail suspension test, and open field test, speculating its use as an anti-obesity agent in obese-depressive animals. Since obese control animals reflected decreased locomotor activity, a positive relationship can be speculated to exist between obesity and depression. Further studies on various antidepressant models are required to confirm this relationship.