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1.
J Cardiothorac Vasc Anesth ; 30(5): 1386-95, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27499346

RESUMO

OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. DESIGN AND SETTING: A systematic review of literature followed by web-based voting on findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from 61 countries. INTERVENTIONS: The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.


Assuntos
Cuidados Críticos/métodos , Medicina Baseada em Evidências/métodos , Mortalidade Hospitalar , Internacionalidade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estado Terminal , Humanos , Médicos
2.
J Chem Theory Comput ; 12(8): 3948-58, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27267665

RESUMO

The need to interpret ultraviolet photoemission data strongly motivates the refinement of first-principles techniques that are able to accurately predict spectral properties. In this work, we employ Koopmans-compliant functionals, constructed to enforce piecewise linearity in approximate density functionals, to calculate the structural and electronic properties of DNA and RNA nucleobases. Our results show that not only ionization potentials and electron affinities are accurately predicted with mean absolute errors of <0.1 eV, but also that calculated photoemission spectra are in excellent agreement with experimental ultraviolet photoemission spectra. In particular, the role and contribution of different tautomers to the photoemission spectra are highlighted and discussed in detail. The structural properties of nucleobases are also investigated, showing an improved description with respect to local and semilocal density-functional theory. Methodologically, our results further consolidate the role of Koopmans-compliant functionals in providing, through orbital-density-dependent potentials, accurate electronic and spectral properties.


Assuntos
DNA/química , Nucleosídeos/química , Espectroscopia Fotoeletrônica , RNA/química , Conformação de Ácido Nucleico , Teoria Quântica
3.
J Cardiothorac Vasc Anesth ; 30(4): 1005-14, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27238433

RESUMO

OBJECTIVE: To comprehensively assess published randomized peer-reviewed studies related to volatile agents used for sedation in intensive care unit (ICU) settings, with the hypothesis that volatile agents could reduce time to extubation in adult patients. DESIGN: Systematic review and meta-analysis of randomized trials. SETTING: Intensive care units. PARTICIPANTS: Critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The BioMedCentral, PubMed, Embase, and Cochrane Central Register databases of clinical trials were searched systematically for studies on volatile agents used in the ICU setting. Articles were assessed by trained investigators, and divergences were resolved by consensus. Inclusion criteria included random allocation to treatment (volatile agents versus any intravenous comparator, with no restriction on dose or time of administration) in patients requiring mechanical ventilation in the ICU. Twelve studies with 934 patients were included in the meta-analysis. The use of halogenated agents reduced the time to extubation (standardized mean difference = -0.78 [-1.01 to -0.55] hours; p for effect<0.00001; p for heterogeneity = 0.18; I(2) = 32% in 7 studies with 503 patients). Results for time to extubation were confirmed in all subanalyses (eg, medical and surgical patients) and sensitivity analyses. No differences in length of hospital stay, ICU stay, and mortality were recorded. CONCLUSIONS: In this meta-analysis of randomized trials, volatile anesthetics reduced time to extubation in medical and surgical ICU patients. The results of this study should be confirmed by large and high-quality randomized controlled studies.


Assuntos
Extubação/estatística & dados numéricos , Anestésicos Inalatórios/farmacologia , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos
4.
Phys Rev Lett ; 114(16): 166405, 2015 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-25955063

RESUMO

The determination of spectral properties from first principles can provide powerful connections between microscopic theoretical predictions and experimental data, but requires complex electronic-structure formulations that fall outside the domain of applicability of common approaches, such as density-functional theory. We show here that Koopmans-compliant functionals, constructed to enforce piecewise linearity and the correct discontinuity derivative in energy functionals with respect to fractional occupation-i.e., with respect to charged excitations-provide molecular photoemission spectra and momentum maps of Dyson orbitals that are in excellent agreement with experimental ultraviolet photoemission spectroscopy and orbital tomography data. These results highlight the role of Koopmans-compliant functionals as accurate and inexpensive quasiparticle approximations to the spectral potential.

5.
Crit Care Med ; 43(8): 1559-68, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25821918

RESUMO

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.


Assuntos
Cuidados Críticos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Feminino , Fibrose/terapia , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipotermia Induzida/mortalidade , Masculino , Estudos Multicêntricos como Assunto , Decúbito Ventral , Reprodutibilidade dos Testes , Projetos de Pesquisa , Respiração Artificial/métodos , Respiração Artificial/mortalidade , Ácido Tranexâmico/sangue
6.
Paediatr Anaesth ; 25(5): 468-76, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25559766

RESUMO

INTRODUCTION: The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50-75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective α2 -agonist with sedative and analgesic properties. A meta-analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children. METHODS: Studies were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials and updated on August 15th, 2014. Primary outcomes were represented by improved sedation at separation from parents, at induction of anesthesia, and reduction in postoperative agitation. Secondary outcomes were reduction in rescue analgesic drugs, and duration of surgery and anesthesia. Inclusion criteria were random allocation to treatment and comparison between dexmedetomidine and midazolam. Exclusion criteria were adult studies, duplicate publications, intravenous administration, and no data on main outcomes. RESULTS: Data from 1033 children in 13 randomized trials were analyzed. Overall, in the dexmedetomidine group there was a higher incidence of satisfactory sedation at separation from parents (314 of 424 [74%] in the dexmedetomidine group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05-1.62], P = 0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of 141 [40%], RR = 0.31 [0.13-0.73], P = 0.008), and a significant reduction in the rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52 [0.39-0.70], P < 0.001). There was no evidence of a higher incidence of satisfactory sedation at anesthesia induction or any reduction of duration of surgery and anesthesia. CONCLUSIONS: Dexmedetomidine is effective in decreasing anxiety upon separation from parents, decreasing postoperative agitation, and providing more effective postoperative analgesia when compared with midazolam.


Assuntos
Dexmedetomidina , Hipnóticos e Sedativos , Midazolam , Medicação Pré-Anestésica/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ansiedade/prevenção & controle , Criança , Humanos , Complicações Pós-Operatórias/prevenção & controle , Agitação Psicomotora/prevenção & controle , Resultado do Tratamento
7.
Curr Pharm Des ; 20(34): 5497-505, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24669970

RESUMO

There is initial evidence, at least in cardiac surgery, that total intra-venous anesthesia (usually a propofol-based total intravenous anesthesia) is associated with an increased mortality when compared to an anesthetic plan including a halogenated anesthetics. The cardiac protective properties of halogenated agents (desflurane, isoflurane and sevoflurane) have not been confirmed in non-cardiac surgery and mixed results exist for patients admitted in postoperative intensive care units. This article summarizes the papers with the most impressive findings in favor of halogenated anesthetics, but it recognizes that, at the same time, there is no evidence based medicine against the use of propofol, highlighting the need for large randomized trials that should focus on survival.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/tendências , Cardiotônicos/administração & dosagem , Éteres Metílicos/administração & dosagem , Propofol/administração & dosagem , Animais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ensaios Clínicos como Assunto/métodos , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Sevoflurano , Fatores de Tempo
8.
J Cardiothorac Vasc Anesth ; 27(6): 1384-98, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24103711

RESUMO

OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING: Systematic literature review and international web-based survey. PARTICIPANTS: More than 300 physicians from 62 countries. INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.


Assuntos
Lesão Renal Aguda/prevenção & controle , Lesão Renal Aguda/terapia , Lesão Renal Aguda/mortalidade , Comorbidade , Pesquisas sobre Serviços de Saúde , Hemodinâmica , Humanos , Internet , Monitorização Intraoperatória , Assistência Perioperatória
9.
Crit Care Resusc ; 15(1): 42-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23432501

RESUMO

OBJECTIVE: To evaluate the efficacy of methylene blue in raising mean arterial pressure in hypotensive patients. DESIGN: A meta-analysis of randomised controlled trials. DATA SOURCES: We searched BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials. DATA EXTRACTION: Inclusion criteria were random allocation to treatment and comparison of methylene blue versus any comparator. Exclusion criteria were duplicate publications, non-adult studies and no data on main outcomes. The primary end point was mean arterial blood pressure value 1 hour after the study drug administration; the secondary end points were mortality at the longest follow-up available, and cardiac index. DATA SYNTHESIS: Data from 174 patients in five randomised controlled studies were analysed. Mean arterial pressure rose in patients receiving methylene blue (weighted mean difference = 6.93 mmHg; 95% CI, 1.67 to 12.18; P for effect = 0.01; P for heterogeneity = 0.17; I2 = 41%). Only two studies reported the values of cardiac index with a non-statistically significant improvement in the methylene blue group (mean difference = 0.76 L/min/m2; 95% CI, ? 0.32 to 1.84; P for effect = 0.2). The overall mortality rate was 16% (14/88) among methylene blue treated patients and 23% (20/86) in the control group (odds ratio = 0.65; 95% CI, 0.21 to 2.08; P for effect = 0.5). CONCLUSIONS: Methylene blue increases arterial blood pressure and systemic vascular resistances in vasoplegic patients without a detrimental effect on survival.


Assuntos
Hipotensão/tratamento farmacológico , Azul de Metileno/uso terapêutico , Vasoconstritores/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
BMJ ; 343: d5701, 2011 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-22012809

RESUMO

OBJECTIVES: To determine the efficacy of intraoperative treatment with low dose tranexamic acid in reducing the rate of perioperative transfusions in patients undergoing radical retropubic prostatectomy. DESIGN: Double blind, parallel group, randomised, placebo controlled trial. SETTING: One university hospital in Milan, Italy. PARTICIPANTS: 200 patients older than 18 years and undergoing radical retropubic prostatectomy agreed to participate in the trial. Exclusion criteria were atrial fibrillation, coronary artery disease treated with drug eluting stent, severe chronic renal failure, congenital or acquired thrombophilia, and known or suspected allergy to tranexamic acid. INTERVENTIONS: Intravenous infusion of tranexamic acid or equivalent volume of placebo (saline) according to the following protocol: loading dose of 500 mg tranexamic acid 20 minutes before surgery followed by continuous infusion of tranexamic acid at 250 mg/h during surgery. PRIMARY OUTCOME: number of patients receiving blood transfusions perioperatively. Secondary outcome: intraoperative blood loss. Six month follow-up to assess long term safety in terms of mortality and thromboembolic events. RESULTS: All patients completed treatment and none was lost to follow-up. Patients transfused were 34 (34%) in the tranexamic acid group and 55 (55%) in the control group (absolute reduction in transfusion rate 21% (95% CI 7% to 34%); relative risk of receiving transfusions for patients treated with tranexamic acid 0.62 (0.45 to 0.85); number needed to treat 5 (3 to 14); P = 0.004). At follow-up, no patients died and the occurrence of thromboembolic events did not differ between the two groups. CONCLUSIONS: Intraoperative treatment with low dose tranexamic acid is safe and effective in reducing the rate of perioperative blood transfusions in patients undergoing radical retropubic prostatectomy. Trial registration ClinicalTrials.gov identifier NCT00670345.


Assuntos
Antifibrinolíticos/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Prostatectomia/efeitos adversos , Ácido Tranexâmico/administração & dosagem , Adulto , Transfusão de Sangue , Método Duplo-Cego , Seguimentos , Humanos , Cuidados Intraoperatórios , Masculino , Resultado do Tratamento
11.
Phys Rev Lett ; 102(6): 066806, 2009 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-19257622

RESUMO

Electron quasiparticles are progressively weakened by correlations upon approaching a continuos Mott metal-insulator transition in a bulk solid. We show that corresponding to the bulk weakening, a dead layer forms below the surface of the solid, where quasiparticles are exponentially suppressed. The surface dead layer depth is a bulk property and diverges when the Mott transition is approached. We describe this phenomenon in a Hubbard model within a self-consistent Gutzwiller approximation. The photoemission data of Rodolakis et al. [Phys. Rev. Lett. 102, 066805 (2009)] in V2O3 appear to be in accord with this physical picture.

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