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1.
Hum Vaccin Immunother ; 19(1): 2209001, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37249310

RESUMO

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Neutralizantes , Anticorpos Antivirais , Método Duplo-Cego , População do Leste Asiático , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Imunogenicidade da Vacina , Infecções por Papillomavirus/prevenção & controle , Vacinas Combinadas
2.
Vaccine ; 41(19): 3141-3149, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37061370

RESUMO

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinas de Partículas Semelhantes a Vírus , Feminino , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , China , Método Duplo-Cego , População do Leste Asiático , Papillomavirus Humano , Imunogenicidade da Vacina , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
3.
Hum Vaccin Immunother ; 19(1): 2167438, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36705277

RESUMO

The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection ( SARI) caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.


Assuntos
COVID-19 , Pneumonia , Vacinas , Chlorocebus aethiops , Animais , Humanos , Malásia/epidemiologia , Células Vero , Estudos Retrospectivos , COVID-19/prevenção & controle , SARS-CoV-2
4.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5383-5388, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36472046

RESUMO

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.


Assuntos
Medicina Tradicional Tibetana , Pesquisa Farmacêutica , Tibet , Controle de Qualidade , Indústria Farmacêutica
5.
J Nucl Med ; 63(4): 556-559, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34475235

RESUMO

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Anticorpos Monoclonais , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Artéria Hepática/patologia , Humanos , Radioisótopos do Iodo , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia , Estudos Prospectivos , Resultado do Tratamento
6.
Signal Transduct Target Ther ; 6(1): 194, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001849

RESUMO

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.


Assuntos
Anticorpos Monoclonais Humanizados , Tratamento Farmacológico da COVID-19 , COVID-19/metabolismo , Pulmão/metabolismo , SARS-CoV-2/metabolismo , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , COVID-19/patologia , Método Duplo-Cego , Feminino , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade
7.
Biomed Environ Sci ; 33(7): 484-492, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32807267

RESUMO

OBJECTIVE: Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection. METHODS: Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted. RESULTS: A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination. CONCLUSIONS: Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vacinas contra Hepatite A/administração & dosagem , Hepatite A/imunologia , Imunidade Ativa , Vacinação , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Modelos Estatísticos , Vacinação/estatística & dados numéricos
8.
Zhongguo Zhong Yao Za Zhi ; 45(13): 2993-3000, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726003

RESUMO

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Pandemias , Pneumonia Viral , Adolescente , Adulto , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19
9.
World J Gastroenterol ; 26(15): 1805-1819, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32351295

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with intermediate hepatocellular carcinoma (HCC) according to treatment guidelines. However, a large number of patients with advanced HCC also receive TACE in clinical practice, especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score (ECOG) 1. In view of previous studies, such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread; therefore, patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment, but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking. AIM: To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model. METHODS: Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016. Overall survival (OS) was estimated using Kaplan-Meier curves and compared by the log-rank test. Multivariate Cox regression was used to develop the potential prognostic models. The discriminatory ability of the models was compared and validated in various patient subgroups. The individual survival prediction for six-and-twelve (6&12) criteria, defined as the algebraic sum of tumor size (cm) and tumor number, was illustrated by contour plot of 3-year survival probability and nomogram. RESULTS: A total of 792 eligible patients were included. During follow-up, median OS reached 18.9 mo [95% confidence interval (CI): 16.9-21.0]. Three independent multivariate analyses demonstrated that tumor size, tumor number, α-fetoprotein level, albumin-bilirubin grade and total bilirubin were prognostic factors of OS (P < 0.05). The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability. In addition, the 6&12 criteria was correlated with OS in various subgroups of patients. The patients were stratified into three strata with score ≤ 6, > 6 but ≤ 12, and > 12 with different median OS of 39.8 mo (95%CI: 23.9-55.7), 21.1 mo (95%CI: 18.4-23.8) and 9.8 mo (95%CI: 8.3-11.3), respectively (P < 0.001). CONCLUSION: TACE is effective for advanced HCC patients with ECOG 1 alone, and the 6&12 criteria may help with clinical decision-making.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Quimioembolização Terapêutica/métodos , Tomada de Decisão Clínica/métodos , Neoplasias Hepáticas/diagnóstico , Nomogramas , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Tumoral
10.
World J Gastroenterol ; 26(6): 657-669, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103874

RESUMO

BACKGROUND: The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM: To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS: This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS: All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION: Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/mortalidade , Regras de Decisão Clínica , Neoplasias Hepáticas/mortalidade , Índice de Gravidade de Doença , Idoso , Área Sob a Curva , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Carga Tumoral , alfa-Fetoproteínas/análise
12.
Biomed Environ Sci ; 32(8): 614-623, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31488237

RESUMO

OBJECTIVE: To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes. METHODS: The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions. RESULTS: Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions. CONCLUSION: The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.


Assuntos
Ensaios Clínicos como Assunto/métodos , Soluções Oftálmicas/farmacocinética , Administração Tópica , Estudos Cross-Over , Humanos , Modelos Teóricos , Tamanho da Amostra , Equivalência Terapêutica
13.
BMJ Open ; 6(10): e012488, 2016 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-27798013

RESUMO

INTRODUCTION: The invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7). METHODS AND ANALYSIS: 1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12-15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed. ETHICS AND DISSEMINATION: Ethics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance. TRIAL REGISTRATION NUMBER: NCT02736240.


Assuntos
Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Imunogenicidade da Vacina/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , China/epidemiologia , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Infecções Pneumocócicas/imunologia , Segurança , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/administração & dosagem
14.
Expert Rev Vaccines ; 15(1): 129-37, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26460695

RESUMO

OBJECTIVES: To evaluate the efficacy and immunogenicity of the Sinovac Enterovirus 71 (EV71) vaccine for up to two years. METHODS: We did a follow-up study of our initial randomized trial in 10,077 participants, who were randomized to receive EV71 vaccine or placebo in a 1:1 ratio and followed for 14 months. The extended follow-up study lasted for another 12 months and EV71-associated hand, foot, and mouth disease (HFMD) was the primary endpoint. RESULTS: The EV71 vaccine showed an efficacy of 95.1% (95%CI 63.6, 99.3) against EV71-associated HFMD during the extended follow-up and an overall efficacy of 94.7% (95%CI 87.8, 97.6) for two years. The EV71 vaccine elicited a sustained high level of neutralizing antibodies in participants, and no serious adverse event was judged to be related to the vaccination. CONCLUSION: The Sinovac EV71 vaccine could provide a sustained high protection against EV71-associated HFMDs for up to 2 years.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Pré-Escolar , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Placebos/administração & dosagem , Resultado do Tratamento , Vacinas Virais/efeitos adversos
15.
Yao Xue Xue Bao ; 50(11): 1402-7, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26911032

RESUMO

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.


Assuntos
Ensaios Clínicos como Assunto , Coleta de Dados/métodos , Projetos de Pesquisa , Coleta de Dados/normas , Humanos , Modelos Teóricos
16.
Yao Xue Xue Bao ; 50(11): 1464-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26911044

RESUMO

Testing of hypothesis was affected by statistical analysis set division which was an important data management work before data base lock-in. Objective division of statistical analysis set under blinding was the guarantee of scientific trial conclusion. All the subjects having accepted at least once trial treatment after randomization should be concluded in safety set. Full analysis set should be close to the intention-to-treat as far as possible. Per protocol set division was the most difficult to control in blinded examination because of more subjectivity than the other two. The objectivity of statistical analysis set division must be guaranteed by the accurate raw data, the comprehensive data check and the scientific discussion, all of which were the strict requirement of data management. Proper division of statistical analysis set objectively and scientifically is an important approach to improve the data management quality.


Assuntos
Ensaios Clínicos como Assunto/normas , Projetos de Pesquisa/normas , Estatística como Assunto , Bases de Dados Factuais
17.
World J Gastroenterol ; 20(3): 774-85, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24574750

RESUMO

AIM: To evaluate the effect of the shunting branch of the portal vein (PV) (left or right) and the initial stent position (optimal or suboptimal) of a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We retrospectively reviewed 307 consecutive cirrhotic patients who underwent TIPS placement for variceal bleeding from March 2001 to July 2010 at our center. The left PV was used in 221 patients and the right PV in the remaining 86 patients. And, 224 and 83 patients have optimal stent position and sub-optimal stent positions, respectively. The patients were followed until October 2011 or their death. Hepatic encephalopathy, shunt dysfunction, and survival were evaluated as outcomes. The difference between the groups was compared by Kaplan-Meier analysis. A Cox regression model was employed to evaluate the predictors. RESULTS: Among the patients who underwent TIPS to the left PV, the risk of hepatic encephalopathy (P = 0.002) and mortality were lower (P < 0.001) compared to those to the right PV. Patients who underwent TIPS with optimal initial stent position had a higher primary patency (P < 0.001) and better survival (P = 0.006) than those with suboptimal initial stent position. The shunting branch of the portal vein and the initial stent position were independent predictors of hepatic encephalopathy and shunt dysfunction after TIPS, respectively. And, both were independent predictors of survival. CONCLUSION: TIPS placed to the left portal vein with optimal stent position may reduce the risk of hepatic encephalopathy and improve the primary patency rates, thereby prolonging survival.


Assuntos
Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/cirurgia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/instrumentação , Stents , Adulto , Idoso , Distribuição de Qui-Quadrado , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/mortalidade , Varizes Esofágicas e Gástricas/fisiopatologia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/fisiopatologia , Encefalopatia Hepática/etiologia , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Hipertensão Portal/mortalidade , Hipertensão Portal/fisiopatologia , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Flebografia , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/mortalidade , Portografia , Modelos de Riscos Proporcionais , Falha de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
J Infect Dis ; 209(1): 46-55, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23922377

RESUMO

BACKGROUND: Vaccination is considered a top priority for the control of human enterovirus 71 (EV71) infection outbreaks. METHODS: On the basis of phase I trial results, we conducted a double-blind, randomized, controlled trial to evaluate the optimal dose, immunogenicity, safety and immune persistence of the vaccine. A total of 480 healthy infants were randomly assigned to receive 2 injections of 100 U of vaccine, 200 U of vaccine, 400 U of vaccine, or placebo. Solicited adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each vaccination were collected for safety evaluation. Blood samples were collected for neutralizing antibody assay. RESULTS: EV71 vaccine was well tolerated, and no dose-related safety concerns were observed. Two doses of the vaccine yielded seropositivity frequencies of 92.3%, 95.9%, and 99.0% (with titers ≥1:8) in the 100 U, 200 U, and 400 U groups, respectively. Geometric mean titers measured by neutralizing antibody assay increased to 60.2 (95% confidence interval [CI], 41.9-86.4), 72.8 (95% CI, 50.8-104.3), and 252.1 (95% CI, 180.8-351.6) for the 100 U, 200 U, and 400 U groups, respectively. The dose-response relationship, with the 400 U dose showing higher immunogenicity than the 100 U and 200 U doses, remained until 13 months after the second vaccination, despite waning antibody levels. CONCLUSIONS: The 400 U dose was recommended as the optimal dose for the phase III trial because of its good safety profile and higher immunogenicity.


Assuntos
Enterovirus Humano A/imunologia , Vacinas Virais/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Memória Imunológica/imunologia , Lactente , Masculino , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
19.
Clin Vaccine Immunol ; 20(12): 1805-11, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24108780

RESUMO

The determination of lot-to-lot consistency in the manufacturing process is a mandatory step in the clinical development of the novel enterovirus 71 (EV71) vaccine. A phase III, randomized, placebo-controlled, double-blind trial assessed the lot consistency, immunogenicity, and safety of the EV71 vaccine in children aged 6 to 59 months. Healthy children (n = 1,400) received one of three lots of the EV71 vaccine containing 400 U of EV71 antigen or a placebo at days 0 and 28. Blood samples were collected before dose 1 and at 28 days after dose 2 (day 56) for an anti-EV71 neutralizing antibody (NTAb) assay. The geometric mean titer (GMT) and the seropositivity rates (with titers of ≥1:8) were compared at day 56. After each dose, the solicited injection site and general adverse events (AEs) were recorded for 7 days, and unsolicited AEs were recorded for 28 days. At day 56, the seropositivity rates ranged from 99.7% to 100% for the vaccine groups. The NTAb GMTs for the vaccine were 140.3 (95% confidence interval [CI], 117.8 to 167.1), 141.5 (95% CI, 118.0 to 169.6), and 146.6 (95% CI, 122.5 to 175.3). The two-sided 95% CI of the log difference in GMTs between the pairs of lots were between -0.176 and 0.176, therefore meeting the predefined equivalence criteria. The percentages of subjects reporting any injection site AEs, general AEs, or serious AEs were similar across the four vaccination groups. In conclusion, the demonstration of consistency between the manufacturing lots confirms for the purposes of clinical development the reliability of the EV71 vaccine production process. (This study has been registered at ClinicalTrials.gov under registration no. NCT01636245.).


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/imunologia , Pré-Escolar , China , Método Duplo-Cego , Infecções por Enterovirus/imunologia , Feminino , Humanos , Lactente , Masculino , Placebos , Vacinação/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos
20.
J Dig Dis ; 14(4): 181-90, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23324079

RESUMO

OBJECTIVE: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib in combination with transarterial chemoembolization (TACE) vs TACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma. METHODS: A total of 304 patients were enrolled, in which 82 received concurrent sorafenib (400 mg orally twice daily, initiated within 14 days after TACE), and these patients were matched with 164 patients who received TACE alone at a 1:2 ratio using propensity score matching to minimize selection bias. The response to treatment, time-to-progression (TTP), overall survival (OS) as well as adverse events were compared between the two groups. RESULTS: During a median follow-up period of 21.4 weeks (range 0.5-103 weeks), the addition of sorafenib prolonged TTP (6.3 vs 4.3 months; hazard ratio [HR] 0.60, 95% CI 0.422-0.853, P = 0.004) and median survival (7.5 vs 5.1 months; HR 0.61, 95% CI 0.423-0.884, P = 0.009) compared with TACE alone. Significant prognostic factors for OS by multivariate analysis included the use of sorafenib, Barcelona Clinic Liver Cancer stage, metastasis/vascular invasion and Child-Pugh score. CONCLUSIONS: The combined use of sorafenib and TACE was generally well tolerated and significantly improved OS and TTP compared with TACE alone in patients with intermediate or advanced HCC. Further studies are warranted to confirm the safety and efficacy of this combination therapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Administração Oral , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Prognóstico , Pontuação de Propensão , Estudos Prospectivos , Sorafenibe , Análise de Sobrevida , Resultado do Tratamento
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