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1.
PLoS Biol ; 20(1): e3001525, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35041657

RESUMO

[This corrects the article DOI: 10.1371/journal.pbio.3001133.].

2.
PLoS Biol ; 19(11): e3001133, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34813595

RESUMO

Alongside the growing concerns regarding predatory journal growth, other questionable editorial practices have gained visibility recently. Among them, we explored the usefulness of the Percentage of Papers by the Most Prolific author (PPMP) and the Gini index (level of inequality in the distribution of authorship among authors) as tools to identify journals that may show favoritism in accepting articles by specific authors. We examined whether the PPMP, complemented by the Gini index, could be useful for identifying cases of potential editorial bias, using all articles in a sample of 5,468 biomedical journals indexed in the National Library of Medicine. For articles published between 2015 and 2019, the median PPMP was 2.9%, and 5% of journal exhibited a PPMP of 10.6% or more. Among the journals with the highest PPMP or Gini index values, where a few authors were responsible for a disproportionate number of publications, a random sample was manually examined, revealing that the most prolific author was part of the editorial board in 60 cases (61%). The papers by the most prolific authors were more likely to be accepted for publication within 3 weeks of their submission. Results of analysis on a subset of articles, excluding nonresearch articles, were consistent with those of the principal analysis. In most journals, publications are distributed across a large number of authors. Our results reveal a subset of journals where a few authors, often members of the editorial board, were responsible for a disproportionate number of publications. To enhance trust in their practices, journals need to be transparent about their editorial and peer review practices.


Assuntos
Comportamento , Viés , Pesquisa Biomédica , Políticas Editoriais , Publicações Periódicas como Assunto , Inquéritos e Questionários , National Library of Medicine (U.S.) , Estados Unidos
3.
BMC Med Res Methodol ; 24(1): 93, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649798

RESUMO

BACKGROUND: The dissemination of clinical trial results is an important scientific and ethical endeavour. This survey of completed interventional studies in a French academic center describes their reporting status. METHODS: We explored all interventional studies sponsored by Rennes University Hospital identified on the French Open Science Monitor which tracks trials registered on EUCTR or clinicaltrials.gov, and provides an automatic assessment of the reporting of results. For each study, we ascertained the actual reporting of results using systematic searches on the hospital internal database, bibliographic databases (Google Scholar, PubMed), and by contacting all principal investigators (PIs). We describe several features (including total budget and numbers of trial participants) of the studies that did not report any results. RESULTS: The French Open Science Monitor identified 93 interventional studies, among which 10 (11%) reported results. In contrast, our survey identified 36 studies (39%) reporting primary analysis results and an additional 18 (19%) reporting results for secondary analyses (without results for their primary analysis). The overall budget for studies that did not report any results was estimated to be €5,051,253 for a total of 6,735 trial participants. The most frequent reasons for the absence of results reported by PIs were lack of time for 18 (42%), and logistic difficulties (e.g. delay in obtaining results or another blocking factor) for 12 (28%). An association was found between non-publication and negative results (adjusted Odds Ratio = 4.70, 95% Confidence Interval [1.67;14.11]). CONCLUSIONS: Even allowing for the fact that automatic searches underestimate the number of studies with published results, the level of reporting was disappointingly low. This amounts to a waste of trial participants' implication and money. Corrective actions are needed. TRIAL REGISTRATION: https://osf.io/q5hcs.


Assuntos
Ensaios Clínicos como Assunto , Humanos , Centros Médicos Acadêmicos/estatística & dados numéricos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/economia , França , Projetos de Pesquisa , Inquéritos e Questionários , Estudos Transversais
4.
Int J Cancer ; 152(12): 2474-2484, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36779785

RESUMO

Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics. Effects on overall survival (OS), progression-free survival and tumor response were summarized in meta-analyses. Effects on QoL were qualitatively summarized. Between 2000 and 2020, the FDA approved 145 novel cancer drugs for 156 indications based on 190 clinical trials. Half of indications (49%) were approved without RCT evidence; 82% had a single clinical trial only. OS was primary endpoint in 14% of trials and QoL data were available from 25%. The median OS benefit was 2.55 months (IQR, 1.33-4.28) with a mean hazard ratio for OS of 0.75 (95%CI, 0.72-0.79, I2  = 42). Improvement for QoL was reported for 7 (4%) of 156 indications. Over time, priority review was used increasingly and the mean number of trials per indication decreased from 1.45 to 1.12. More trials reported results on QoL (19% in 2000-2005; 41% in 2016-2020). For 21 years, novel cancer drugs have typically been approved based on one single, often uncontrolled, clinical trial, measuring surrogate endpoints. This leaves cancer patients without solid evidence that novel drugs improve their survival or QoL and there is no indication towards improvement.


Assuntos
Antineoplásicos , Neoplasias , Estados Unidos , Humanos , United States Food and Drug Administration , Aprovação de Drogas , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Preparações Farmacêuticas
5.
Crit Care ; 27(1): 381, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37784110

RESUMO

BACKGROUND: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients. METHODS: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6). RESULTS: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected. CONCLUSION: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).


Assuntos
Sepse , Choque Séptico , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Escores de Disfunção Orgânica , Choque Séptico/complicações , Citrulina/farmacologia , Citrulina/uso terapêutico , Insuficiência de Múltiplos Órgãos/etiologia , Estado Terminal/terapia , Respiração Artificial/efeitos adversos , Sepse/tratamento farmacológico , Sepse/complicações , Unidades de Terapia Intensiva , Suplementos Nutricionais , Arginina/uso terapêutico
6.
BMC Med ; 20(1): 177, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35590360

RESUMO

BACKGROUND: Transparency and reproducibility are expected to be normative practices in clinical trials used for decision-making on marketing authorisations for new medicines. This registered report introduces a cross-sectional study aiming to assess inferential reproducibility for main trials assessed by the European Medicines Agency. METHODS: Two researchers independently identified all studies on new medicines, biosimilars and orphan medicines given approval by the European Commission between January 2017 and December 2019, categorised as 'main studies' in the European Public Assessment Reports (EPARs). Sixty-two of these studies were randomly sampled. One researcher retrieved the individual patient data (IPD) for these studies and prepared a dossier for each study, containing the IPD, the protocol and information on the conduct of the study. A second researcher who had no access to study reports used the dossier to run an independent re-analysis of each trial. All results of these re-analyses were reported in terms of each study's conclusions, p-values, effect sizes and changes from the initial protocol. A team of two researchers not involved in the re-analysis compared results of the re-analyses with published results of the trial. RESULTS: Two hundred ninety-two main studies in 173 EPARs were identified. Among the 62 studies randomly sampled, we received IPD for 10 trials. The median number of days between data request and data receipt was 253 [interquartile range 182-469]. For these ten trials, we identified 23 distinct primary outcomes for which the conclusions were reproduced in all re-analyses. Therefore, 10/62 trials (16% [95% confidence interval 8% to 28%]) were reproduced, as the 52 studies without available data were considered non-reproducible. There was no change from the original study protocol regarding the primary outcome in any of these ten studies. Spin was observed in the report of one study. CONCLUSIONS: Despite their results supporting decisions that affect millions of people's health across the European Union, most main studies used in EPARs lack transparency and their results are not reproducible for external researchers. Re-analyses of the few trials with available data showed very good inferential reproducibility. TRIAL REGISTRATION: https://osf.io/mcw3t/.


Assuntos
Medicamentos Biossimilares , Aprovação de Drogas , Estudos Transversais , Humanos , Disseminação de Informação , Reprodutibilidade dos Testes
7.
BMC Cancer ; 22(1): 381, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397511

RESUMO

BACKGROUND: Tivozanib (Fotivda) is an anti-angiogenic tyrosine kinase inhibitor that was denied access to the US market by the Food and Drug Administration (FDA). In contrast, it was granted approval by the European Medicines Agency (EMA) for the treatment of Renal Cell Carcinoma in adults. Given the conflicting decisions from these regulatory agencies, the objectives of the following study are (i) to critically review the evidence supporting the approval of tivozanib; (ii) to analyse the dissemination of this evidence in the literature by way of a citation analysis. METHODS: Pivotal trials were searched by two independent reviewers using Medline, Cochrane Library, ClinicalTrials.gov and the European Public Assessment Report. The risk of bias for each trial was then inductively assessed. Articles citing any of these trials were identified using Web of Sciences. Finally, the quality of the citations was evaluated by two independent reviewers according to standard data extraction methods. RESULTS: The search for primary evidence identified two pivotal studies: TIVO-1 upon which the FDA and the EMA decisions were based, and TIVO-3 which was conducted after the agencies' decisions had been issued. The TIVO-1 trial presented several limitations that compromised causal inference, in relation to (i) design (absence of blinding, inappropriate comparator, and one-way crossover), (ii) poor internal consistency in the results for the primary endpoint, (iii) a discrepancy between a benefit observed for progression-free survival (HR: 0.80, 95% CI [0.64-0.99]) and the absence of difference for overall survival (HR: 1.25, 95% CI [0.95 - 1.62]). Our citation search protocol identified 229 articles that cited TIVO-1 in the 7 years following its publication, among which 151 (65.9%) citing articles discussing efficacy. Presence of spin was identified in 64 (42.4%) of these 151 citing articles, and 39 (25.8%) additional articles citing results without providing enough elements to interpret the TIVO-1 results. CONCLUSION: EMA's approval was based on a single pivotal trial presenting critical limitations, rendering the results from the trial potentially inconclusive. The broad dissemination of TIVO-1 results in the scientific literature may have been affected by spin or results were presented in an inadequate critical manner.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Quinolinas , Adulto , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico
8.
Ann Surg ; 273(1): 49-56, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209911

RESUMO

OBJECTIVE: To answer whether synchronous colorectal cancer liver metastases (SLM) should be resected simultaneously with primary cancer or should be delayed. SUMMARY BACKGROUND DATA: Numerous studies have compared both strategies. All were retrospective and conclusions were contradictory. METHODS: Adults with colorectal cancer and resectable SLM were randomly assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the rate of major complications within 60 days following surgery. Secondary outcomes included overall and disease-free survival. RESULTS: A total of 105 patients were recruited. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups, respectively) were analyzed. The percentage of major perioperative complications did not differ between groups (49% and 46% in the simultaneous- and delayed-resection groups, respectively, adjusted OR 0.84, 95% CI 0.35-2.01; P = 0.70, logistic regression). Complications rates were 28% and 13% (P = 0.08, χ2 test) at colorectal site and 15% and 17% (P = 0.80, χ2 test) at liver site, in simultaneous- and delayed-resection groups, respectively. In the delayed-resection group, 8 patients did not reach the liver resection stage, and this was due to disease progression in 6 cases. After 2 years, overall and disease-free survival tended to be improved in simultaneous as compared with delayed-resection groups (P = 0.05), a tendency which persisted for OS after a median follow-up of 47 months. CONCLUSIONS: Complication rates did not appear to differ when colorectal cancer and synchronous liver metastases are resected simultaneously. Delayed resection tended to impair overall survival.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Idoso , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Taxa de Sobrevida , Fatores de Tempo
9.
J Antimicrob Chemother ; 76(9): 2234-2236, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34075390

RESUMO

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, clinical trials on antiviral or symptomatic drugs have been conducted very rapidly even for drugs with a poor pharmacological rationale for efficacy on SARS-CoV-2. Despite lacking basic pharmacological information, most of these clinical trials were also extremely redundant. Applying simple rules, (such as identifying a mechanistic rationale, confirming the ability to reach exposure targets at therapeutic dosage and ensuring tests show drug efficacy in appropriate in vitro and animal models before entering clinical trials) might have saved considerable amounts of time and money, and might have avoided useless research. Moreover, combining these simple rules with the implementation of a relevant policy at both an international and a national level, by limiting studies with a poor methodological/scientific approach and aggregating studies with similar design into single clinical trials, is potentially a far more-efficient strategy.


Assuntos
COVID-19 , Pandemias , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , SARS-CoV-2
10.
Liver Transpl ; 27(3): 349-362, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33237618

RESUMO

Few studies have evaluated the efficacy or the cost of hypothermic oxygenated perfusion (HOPE) in the conservation of extended criteria donor (ECD) grafts from donation after brain death (DBD) donors during liver transplantation (LT). We performed a prospective, monocentric study (NCT03376074) designed to evaluate the interest of HOPE for ECD-DBD grafts. For comparison, a control group was selected after propensity score matching among patients who received transplants between 2010 and 2017. Between February and November 2018, the HOPE procedure was used in 25 LTs. Immediately after LT, the median aspartate aminotransferase (AST) level was significantly lower in the HOPE group (724UI versus 1284UI; P = 0.046) as were the alanine aminotransferase (ALT; 392UI versus 720UI; P = 0.01), lactate (2.2 versus 2.7; P = 0.01) There was a significant reduction in intensive care unit stay (3 versus 5 days; P = 0.01) and hospitalization (15 versus 20 days; P = 0.01). The incidence of early allograft dysfunction (EAD; 28% versus 42%; P = 0.22) was similar . A level of AST or ALT in perfusate >800UI was found to be highly predictive of EAD occurrence (areas under the curve, 0.92 and 0.91, respectively). The 12-month graft (88% versus 89.5%; P = 1.00) and patient survival rates (91% versus 91.3%; P = 1.00) were similar. The additional cost of HOPE was estimated at € 5298 per patient. The difference between costs and revenues, from the hospital's perspective, was not different between the HOPE and control groups (respectively, € 3023 versus € 4059]; IC, -€ 5470 and € 8652). HOPE may improve ECD graft function and reduce hospitalization stay without extra cost. These results must be confirmed in a randomized trial.


Assuntos
Transplante de Fígado , Sobrevivência de Enxerto , Hospitalização , Humanos , Fígado/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Preservação de Órgãos , Perfusão , Estudos Prospectivos , Doadores de Tecidos
11.
Br J Haematol ; 191(3): 497-504, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32860711

RESUMO

Morphological features of eosinophils in patients with reactive eosinophilia (28 patients) and clonal eosinophilia (26 patients) have been compared with each other and with the eosinophil characteristics of healthy volunteers (three subjects) and of patients with the idiopathic hypereosinophilic syndrome (three patients). Morphological features, assessed in isolation from other haematological abnormalities, were found to have poor specificity for a myeloid neoplasm. The most useful feature was the presence of basophilic granules in mature eosinophils, which was associated particularly with acute myeloid leukaemia with inv(16). Marked reduction in granules occurred more often in some subsets of the myeloid neoplasm group but nevertheless was lacking in specificity since it was not infrequently seen in reactive eosinophilia. Although experienced morphologists more often considered that a myeloid neoplasm was likely in patients in whom this was the diagnosis (69%), myeloid neoplasia was also considered likely in a considerable proportion (39%) of patients with reactive eosinophilia. Morphological abnormalities of eosinophils therefore cannot be assessed in isolation in seeking to make a diagnosis of a myeloid neoplasm. Morphology is, however, needed and should be integrated with the results of other investigations.

12.
Ann Vasc Surg ; 56: 246-253, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30278260

RESUMO

BACKGROUND: The resting ankle-brachial index (ABI) is a clinical test to diagnose peripheral artery disease. The Wyatt's score has been proposed to assess the students' performance on ABI measurement on a healthy volunteer (HV). No study has shown that this score is sensitive to different teaching methods. In this randomized controlled trial, we wanted to determine whether didactic learning alone or didactic learning combined with experiential learning improves proficiency in the ABI procedure assessed by the Wyatt's score. METHODS: Medical students (n = 30) received a didactic learning, including (1) a presentation of the ABI guidelines and (2) a video demonstration. Each student was then randomized into 2 groups ("the no experiential learning group" and "the experiential learning group"). An initial evaluation was performed after the didactic learning and then the final evaluation at the end of the intervention. A student was considered to be proficient when he performed a correct ABI procedure on an HV. The correct procedure corresponds to the following: (1) correctly answered Wyatt's score and (2) a difference in the ABI measurement between a professor in vascular medicine and a student was ≤0.15. RESULTS: No student was proficient at the initial evaluation. At the final evaluation, there was a significant difference between the number of proficient students for the Wyatt's score depending on their learning group [didactic alone (1/10) or didactic + experiential training (15/20)] and also for the ABI procedure [didactic alone (0/10) or didactic + experiential training (16/20)]. At 6 months, among the 12 students who passed the final evaluation, 4 students passed both the Wyatt's score and the ABI measurement. CONCLUSIONS: Our study demonstrates that the Wyatt's score was sensitive to an educational intervention and no improvement was found in the case of "no experiential learning." The Wyatt's score could be used to evaluate the student on ABI measurement after an educational intervention. TRIAL REGISTRATION: A randomized controlled trial was conducted in the Vascular Medicine Department of Rennes University Hospital (France). This was approved by the ethics review board of our institution (no. 16.150).


Assuntos
Índice Tornozelo-Braço , Educação de Graduação em Medicina/métodos , Doença Arterial Periférica/diagnóstico , Aprendizagem Baseada em Problemas , Estudantes de Medicina , Competência Clínica , Avaliação Educacional , Escolaridade , França , Humanos , Variações Dependentes do Observador , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo
13.
Liver Transpl ; 23(2): 174-183, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27706895

RESUMO

During orthotopic liver transplantation (OLT), clamping of the portal vein induces splanchnic venous congestion and accumulation of noxious compounds. These adverse effects could increase ischemia/reperfusion injury and subsequently the risk of graft dysfunction, especially for grafts harvested from extended criteria donors (ECDs). Temporary portocaval shunt (TPCS) could prevent these complications. Between 2002 and 2013, all OLTs performed in our center were retrospectively analyzed and a propensity score matching analysis was used to compare the effect of TPCS in 686 patients (343 in each group). Patients in the TPCS group required fewer intraoperative transfusions (median number of packed red blood cells-5 versus 6; P = 0.02; median number of fresh frozen plasma-5 versus 6; P = 0.02); had improvement of postoperative biological parameters (prothrombin time, Factor V, international normalized ratio, alkaline phosphatase, and gamma-glutamyltransferase levels); and showed significant reduction of biliary complications (4.7% versus 10.2%; P = 0.006). Survival analysis revealed that TPCS improved 3-month graft survival (94.2% versus 88.6%; P = 0.01) as well as longterm survival of elderly (ie, age > 70 years) donor grafts (P = 0.02). In conclusion, the use of TPCS should be recommended especially when considering an ECD graft. Liver Transplantation 23 174-183 2017 AASLD.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Fígado/efeitos adversos , Derivação Portocava Cirúrgica/métodos , Traumatismo por Reperfusão/prevenção & controle , Adolescente , Adulto , Fatores Etários , Idoso , Transfusão de Sangue , Seleção do Doador/métodos , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Veia Porta/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Veia Cava Inferior/cirurgia , Adulto Jovem , gama-Glutamiltransferase
14.
Nutr Cancer ; 68(3): 464-72, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27007018

RESUMO

Perioperative nutrition with supplements containing L-arginine, ω3-polyunsaturated fatty acids, and nucleotides could boost liver function recovery, immune response, and resistance to infection after hepatic resection. We conducted a placebo-controlled, randomized, double-blind study to assess the effect of a perioperative nutritional supplementation with Oral Impact® in patients undergoing hepatic surgery for liver cancer. Treatment was given three times daily for 7 days before and 3 days after surgery. Primary outcome was factor V, 3 days after surgery. Thirty-five patients (placebo: 17; Oral Impact: 18) were included. Five patients (placebo: three; Oral Impact: two) were not operated and five (placebo: two; Oral Impact: three) did not undergo hepatic resection. Factor V (mean ± SD) was 70 ± 27% and 79 ± 25% (P = 0.409) 3 days after surgery and 90 ± 30% and 106 ± 16% (P = 0.066) 5 days after surgery, in placebo and Oral Impact groups, respectively. There were no significant differences between groups on other outcomes assessing liver function recovery (bile production, γ-glutamyl transferase, α-fetoprotein), immune response (CD3, CD4, CD8 cells, CD4/CD8 ratio, natural killer cells, B lymphocytes), number of infections, and tolerance. A 10-day perioperative nutritional supplementation with Oral Impact does not improve hepatic function, immune response, and resistance to infection in patients undergoing hepatic surgery for liver cancer.


Assuntos
Suplementos Nutricionais , Neoplasias Hepáticas/cirurgia , Assistência Perioperatória/métodos , Administração Oral , Idoso , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Fator V/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Placebos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
15.
Semin Immunol ; 23(1): 42-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21295491

RESUMO

Dendritic cells (DCs) are central to the initiation of tumor-specific immune responses. However, the tumor microenvironment generates immunosuppressive cells and soluble mediators that compromise DC functions and limit the success of DC-based therapies. Progress in understanding DC metabolism in cancer is uncovering novel therapeutic targets that could restore DC capacity to prime T cells and trigger effective anticancer responses. Accumulating evidence also indicates that conventional chemo- and radiotherapy protocols can cause DC activation, enhance antigen cross-presentation, selectively eliminate immunosuppressive cells and revert the immunosuppression state caused by cancer, suggesting that relevant chemoimmunotherapy associations could fully exploit DC capacity to trigger anticancer responses. Here, we discuss recent strategies that harness DC against cancer.


Assuntos
Células Dendríticas/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Animais , Antígenos de Neoplasias/imunologia , Antineoplásicos/uso terapêutico , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Modelos Animais de Doenças , Humanos , Imunoterapia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Microambiente Tumoral/imunologia
16.
Semin Immunol ; 22(3): 113-24, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20403709

RESUMO

An attractive, yet hitherto unproven concept predicts that the promotion of tumor regression should elicit the host's immune response against residual tumor cells to achieve an optimal therapeutic effect. In a way, chemo- or radiotherapy must trigger "danger signals" emitted from immunogenic cell death and hence elicit "danger associated molecular patterns" to stimulate powerful anticancer immune responses. Here, based on the recent experimental and clinical evidence, we will discuss the molecular identity of the multiple checkpoints that dictate the success of "immunogenic chemotherapy" at the levels of the drug, of the tumor cell and of the host immune system.


Assuntos
Tratamento Farmacológico , Imunoterapia/métodos , Neoplasias , Radioterapia , Vacinas Anticâncer/imunologia , Humanos , Sistema Imunitário , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Neoplasias/imunologia , Neoplasias/terapia
17.
Therapie ; 79(1): 111-121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38103949

RESUMO

Clinical trials often last several months or even several years. As the trial progresses, it can be tempting to find out whether the data obtained already answers the question posed at the start of the trial in order to stop inclusions or monitoring earlier. However, knowing and taking into account interim results can sometimes compromise the integrity of the results, which is counterproductive. To minimise this risk and ensure that the treatments are assessed reliably, safety and/or efficacy criteria are monitored during the study by a Data Monitoring Committee. After receiving the results confidentially, the Data Monitoring Committee assesses the benefit/risk ratio of the study treatment and recommends that the trial be continued, modified or terminated. Data Monitoring Committee members issuing these recommendations have an important responsibility: a hasty decision to end the trial may lead to inconclusive results unable to answer the initial question and, inversely, delaying the decision to end the trial may expose the subjects to potentially ineffective or even harmful interventions. The Data Monitoring Committee's task is therefore particularly complex. With this in mind, the round table discussion at the Giens workshops was a chance to review the scientific justification for creating Data Monitoring Committees and to recall the need for their members to receive comprehensive training on the complexities of multiple analyses, confidentiality requirements applying to the results and the need for them to be aware that recommendations to end a trial must be based on data that is robust enough to assess the benefit/risk ratio of the treatment studied.


Assuntos
Comitês de Monitoramento de Dados de Ensaios Clínicos , Humanos , Razão de Chances
18.
J Clin Epidemiol ; 162: 98-106, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37648071

RESUMO

OBJECTIVES: To perform an overview of the overlap of systematic reviews (SRs) assessing direct oral anticoagulants and characterize these reviews in terms of bias and methodological quality (PROSPERO: CRD42022316273). STUDY DESIGN AND SETTING: A PubMed-indexed search was performed from inception to January 31, 2022 to identify SRs evaluating direct oral anticoagulants in patients treated for an acute venous thromboembolism. The risk of bias of these SRs was assessed according to the Risk Of Bias In Systematic reviews tool. Redundancy was defined as overlap in terms of the type of population considered, the interventions compared, and the studies included. RESULTS: A total of 144 SRs were evaluated, of which 26 (18.1%) were classified as original, 87 (60.4%) as conceptual replications, and 31 (21.5%) as excessive replications. The risk of bias was high in 19 (73.1%) of the original SRs, 65 (74.7%) of the conceptual replications, and 21 (67.7%) of the excessive replications. Compared to the original SRs, the overall methodological quality was not improved in either conceptual or excessive replications. CONCLUSION: A large number of SRs was classified as replications; a fifth constituted excessive replications. The replications showed no improvement in overall methodological quality compared to the original SRs.


Assuntos
Anticoagulantes , Humanos , Revisões Sistemáticas como Assunto , Viés , Anticoagulantes/uso terapêutico
19.
Cancer Metastasis Rev ; 30(1): 71-82, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21298323

RESUMO

Chemotherapy or radiotherapy could induce various tumor cell death modalities, releasing tumor-derived antigen as well as danger signals that could either be captured for triggering antitumor immune response or ignored. Exploring the interplay among therapeutic drugs, tumor cell death and the immune cells should improve diagnostic, prognostic, predictive, and therapeutic management of tumor. We summarized some of the cell death-derived danger signals and the mechanism for host to sense and response to cell death in the tumor microenvironment. Based on the recent clinical or experimental findings, several strategies have been suggested to improve the immunogenicity of cell death and augment antitumor immunity.


Assuntos
Antineoplásicos/farmacologia , Imunidade/efeitos dos fármacos , Imunidade/efeitos da radiação , Neoplasias/imunologia , Animais , Apresentação de Antígeno/imunologia , Antineoplásicos/uso terapêutico , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Humanos , Sistema Imunitário/efeitos dos fármacos , Imunoterapia Adotiva , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
20.
BMJ Evid Based Med ; 27(3): 133-136, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33785512

RESUMO

During the COVID-19 pandemic, the rush to scientific and political judgements on the merits of hydroxychloroquine was fuelled by dubious papers which may have been published because the authors were not independent from the practices of the journals in which they appeared. This example leads us to consider a new type of illegitimate publishing entity, 'self-promotion journals' which could be deployed to serve the instrumentalisation of productivity-based metrics, with a ripple effect on decisions about promotion, tenure and grant funding, but also on the quality of manuscripts that are disseminated to the medical community and form the foundation of evidence-based medicine.


Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , Pandemias
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