Protocol-directed sedation versus non-protocol-directed sedation to reduce duration of mechanical ventilation in mechanically ventilated intensive care patients (review)

Background : The sedation needs of critically ill patients have been recognized as a core component of critical care and meeting these is vital to assist recovery and ensure humane treatment. There is growing evidence to suggest that sedation requirements are not always optimally managed. Sub-optimal sedation incorporates both under- and over-sedation and has been linked to both short-term (e.g. length of stay) and long-term (e.g. psychological recovery) outcomes. Various strategies have been proposed to improve sedation management and address aspects of assessment as well as delivery of sedation.

Objectives : To assess the effects of protocol-directed sedation management on the duration of mechanical ventilation and other relevant patient outcomes in mechanically ventilated intensive care unit (ICU) patients. We looked at various outcomes and examined the role of bias in order to examine the level of evidence for this intervention.

Search methods : We searched the Cochrane Central Register of Controlled trials (CENTRAL) (2013; Issue 11), MEDLINE (OvidSP) (1990 to November 2013), EMBASE (OvidSP) (1990 to November 2013), CINAHL (BIREME host) (1990 to November 2013), Database of Abstracts of Reviews of Effects (DARE) (1990 to November 2013), LILACS (1990 to November 2013), Current Controlled Trials and US National Institutes of Health Clinical Research Studies (1990 to November 2013), and reference lists of articles. We re-ran the search in October 2014. We will deal with any studies of interest when we update the review.

Selection criteria : We included randomized controlled trials (RCTs) conducted in adult ICUs comparing management with and without protocol-directed sedation.

Data collection and analysis : Two authors screened the titles and abstracts and then the full-text reports identified from our electronic search. We assessed seven domains of potential risk of bias for the included studies. We examined the clinical, methodological and statistical heterogeneity and used the random-effects model for meta-analysis where we considered it appropriate. We calculated the mean difference (MD) for duration of mechanical ventilation and risk ratio (RR) for mortality across studies, with 95% confidence intervals (CI).

Main results : We identified two eligible studies with 633 participants. Both included studies compared the use of protocol-directed sedation, specifically protocols delivered by nurses, with usual care. We rated the risk of selection bias due to random sequence generation low for one study and unclear for one study. The risk of selection bias related to allocation concealment was low for both studies. We also assessed detection and attrition bias as low for both studies while we considered performance bias high due to the inability to blind participants and clinicians in both studies. Risk due to other sources of bias, such as potential for contamination between groups and reporting bias, was considered unclear. There was no clear evidence of differences in duration of mechanical ventilation (MD -5.74 hours, 95% CI -62.01 to 50.53, low quality evidence), ICU length of stay (MD -0.62 days, 95% CI -2.97 to 1.73) and hospital length of stay (MD -3.78 days, 95% CI -8.54 to 0.97) between people being managed with protocol-directed sedation versus usual care. Similarly, there was no clear evidence of difference in hospital mortality between the two groups (RR 0.96, 95% CI 0.71 to 1.31, low quality evidence). ICU mortality was only reported in one study preventing pooling of data. There was no clear evidence of difference in the incidence of tracheostomy (RR 0.77, 95% CI 0.31 to 1.89). The studies reported few adverse event outcomes; one study reported self extubation while the other study reported re-intubation; given this difference in outcomes, pooling of data was not possible. There was significant heterogeneity between studies for duration of mechanical ventilation (I2 = 86%, P value = 0.008), ICU length of stay (I2 = 82%, P value = 0.02) and incidence of tracheostomy (I2 = 76%, P value = 0.04), with one study finding a reduction in duration of mechanical ventilation and incidence of tracheostomy and the other study finding no difference.

Authors' conclusions : There is currently insufficient evidence to evaluate the effectiveness of protocol-directed sedation. Results from the two RCTs were conflicting, resulting in the quality of the body of evidence as a whole being assessed as low. Further studies, taking into account contextual and clinician characteristics in different ICU environments, are necessary to inform future practice. Methodological strategies to reduce the risk of bias need to be considered in future studies.

Constructing optimal prediction intervals by using neural networks and bootstrap method

This brief proposes an efficient technique for the construction of optimized prediction intervals (PIs) by using the bootstrap technique. The method employs an innovative PI-based cost function in the training of neural networks (NNs) used for estimation of the target variance in the bootstrap method. An optimization algorithm is developed for minimization of the cost function and adjustment of NN parameters. The performance of the optimized bootstrap method is examined for seven synthetic and real-world case studies. It is shown that application of the proposed method improves the quality of constructed PIs by more than 28% over the existing technique, leading to narrower PIs with a coverage probability greater than the nominal confidence level.

Improving the quality of prediction intervals through optimal aggregation

Neural networks (NNs) are an effective tool to model nonlinear systems. However, their forecasting performance significantly drops in the presence of process uncertainties and disturbances. NN-based prediction intervals (PIs) offer an alternative solution to appropriately quantify uncertainties and disturbances associated with point forecasts. In this paper, an NN ensemble procedure is proposed to construct quality PIs. A recently developed lower-upper bound estimation method is applied to develop NN-based PIs. Then, constructed PIs from the NN ensemble members are combined using a weighted averaging mechanism. Simulated annealing and a genetic algorithm are used to optimally adjust the weights for the aggregation mechanism. The proposed method is examined for three different case studies. Simulation results reveal that the proposed method improves the average PI quality of individual NNs by 22%, 18%, and 78% for the first, second, and third case studies, respectively. The simulation study also demonstrates that a 3%-4% improvement in the quality of PIs can be achieved using the proposed method compared to the simple averaging aggregation method.

Writing scientific papers, with special reference to evolutionary ecology

© 2015, Springer International Publishing Switzerland. The advancement of science, as well as scientific careers, depends upon good and clear scientific writing. Science is the most democratic of human endeavours because, in principle, anyone can replicate a scientific discovery. In order for this to continue, writing must be clear enough to be understood well enough to allow replication, either in principle or in fact. In this paper I will present data on the publication process in Evolutionary Ecology, use it to illustrate some of the problems in scientific papers, make some general remarks about writing scientific papers, summarise two new paper categories in the journal which will fill gaps that appear to be expanding in the literature, and summarise new journal policies to help mitigate existing problems. Most of the suggestions about writing would apply to any scientific journal.

Sedation protocols to reduce duration of mechanical ventilation in the ICU: a Cochrane Systematic Review

AIMS: Assess the effects of protocol-directed sedation management on the duration of mechanical ventilation and other relevant patient outcomes in mechanically ventilated intensive care unit patients. BACKGROUND: Sedation is a core component of critical care. Sub-optimal sedation management incorporates both under- and over-sedation and has been linked to poorer patient outcomes. DESIGN: Cochrane systematic review of randomized controlled trials. DATA SOURCES: Cochrane Central Register of Controlled trials, MEDLINE, EMBASE, CINAHL, Database of Abstracts of Reviews of Effects, LILACS, Current Controlled Trials and US National Institutes of Health Clinical Research Studies (1990-November 2013) and reference lists of articles were used. REVIEW METHODS: Randomized controlled trials conducted in intensive care units comparing management with and without protocol-directed sedation were included. Two authors screened titles, abstracts and full-text reports. Potential risk of bias was assessed. Clinical, methodological and statistical heterogeneity were examined and the random-effects model used for meta-analysis where appropriate. Mean difference for duration of mechanical ventilation and risk ratio for mortality, with 95% confidence intervals, were calculated. RESULTS: Two eligible studies with 633 participants comparing protocol-directed sedation delivered by nurses vs. usual care were identified. There was no evidence of differences in duration of mechanical ventilation or hospital mortality. There was statistically significant heterogeneity between studies for duration of mechanical ventilation. CONCLUSIONS: There is insufficient evidence to evaluate the effectiveness of protocol-directed sedation as results from the two randomized controlled trials were conflicting.

Accounting for uncertainty in volumes of seabed change measured with repeat multibeam sonar surveys

Seafloors of unconsolidated sediment are highly dynamic features; eroding or accumulating under the action of tides, waves and currents. Assessing which areas of the seafloor experienced change and measuring the corresponding volumes involved provide insights into these important active sedimentation processes. Computing the difference between Digital Elevation Models (DEMs) obtained from repeat Multibeam Echosounders (MBES) surveys has become a common technique to identify these areas, but the uncertainty in these datasets considerably affects the estimation of the volumes displaced. The two main techniques used to take into account uncertainty in volume estimations are the limitation of calculations to areas experiencing a change in depth beyond a chosen threshold, and the computation of volumetric confidence intervals. However, these techniques are still in their infancy and, as a result, are often crude, seldom used or poorly understood. In this article, we explored a number of possible methodological advances to address this issue, including: (1) using the uncertainty information provided by the MBES data processing algorithm CUBE, (2) adapting fluvial geomorphology techniques for volume calculations using spatially variable thresholds and (3) volumetric histograms. The nearshore seabed off Warrnambool harbour - located in the highly energetic southwest Victorian coast, Australia - was used as a test site. Four consecutive MBES surveys were carried out over a four-months period. The difference between consecutive DEMs revealed an area near the beach experiencing large sediment transfers - mostly erosion - and an area of reef experiencing increasing deposition from the advance of a nearby sediment sheet. The volumes of sediment displaced in these two areas were calculated using the techniques described above, both traditionally and using the suggested improvements. We compared the results and discussed the applicability of the new methodological improvements. We found that the spatially variable uncertainty derived from the CUBE algorithm provided the best results (i.e. smaller confidence intervals), but that similar results can be obtained using as a fixed uncertainty value derived from a reference area under a number of operational conditions.

A consumption CAPM with a reference level

We study an intertemporal asset pricing model in which a representative consumer maximizes expected utility derived from both the ratio of his consumption to some reference level and this level itself. If the reference consumption level is assumed to be determined by past consumption levels, the model generalizes the usual habit formation specifications. When the reference level growth rate is made dependent on the market portfolio return and on past consumption growth, the model mixes a consumption CAPM with habit formation together with the CAPM. It therefore provides, in an expected utility framework, a generalization of the non-expected recursive utility model of Epstein and Zin (1989). When we estimate this specification with aggregate per capita consumption, we obtain economically plausible values of the preference parameters, in contrast with the habit formation or the Epstein-Zin cases taken separately. All tests performed with various preference specifications confirm that the reference level enters significantly in the pricing kernel.

FERRITINA: intervalos de referência para adultos no Estado do Rio Grande do Norte

Ferritin is a protein composed of heavy and light chains, non-covalently linked and which accommodates, in its core, thousands of atoms of iron. Furthermore, this protein represents the stock of iron in the body and it is characterized as an acute marker and predictor of diseases, such as iron deficiency anemia, hereditary hemochromatosis and others. Considering the variability of reference values and the analytical methods currently available, the aim of this work was to propose 95% confidence intervals for adults in the State of Rio Grande do Norte, Brazil, after determining the average concentration of serum ferritin for both sexes, beyond its correlation with the age. We analyzed 385 blood samples, collected by venipuncture from individuals residing in the State, after 12-14 hours of fast. The populational sample had 169 men and 216 women between 18-59 years old, which filled a questionnaire on socioeconomic, food habits and accounts about previous and current diseases. The sample collections were itinerant and the results of erythrogram, fasting glucose, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, urea, creatinine, leukocyte count and platelets, beyond C-reactive protein, were issued to each participant, so that, after selection of the apparently healthy individuals, the dosage of serum ferritin was carried out. Statistical analysis was performed using the softwares SPSS 11.0 Windows version, Epi Info 3.3.2 and Graf instant pad (version 3.02), and the random population sample was single (finite population), for which the test of linear correlation and diagram of dispersion were also made. After selection of individuals and determination of serum ferritin, the most discrepant outliers were disregarded (N = 358, Men = 154/Women = 207) and the average value determined for the masculine sex individuals was 167,18 ng / dL; for the feminine sex individuals, the average value obtained was 81,55 ng / dL. Moreover, we found that 25% of men had values < 90,30 ng / dL; 50% ≤ 156,25 ng / dL and 75% ≤ 229,00 ng / dL. In the group of women, 25% had values < 38,80 ng / dL; 50% ≤ 65,00 ng / dL and 75% ≤ 119,00 ng / dL. Through the correlation coefficient (r = 0,23 with p = 0,003), it is possible to suggest the existence of positive linear correlation between age and serum ferritin for men. The correlation coefficient for women (r = 0,16 with p = 0,025) also confirms the existence of positive linear correlation between serum ferritin and age. Considering the analysis carried out and specific methods corroborating with the proposed benchmarks, we concluded that the average value found for men is higher than that found for women. Furthermore, this scenario rises with age for both sexes, and the 95% confidence intervals obtained were 74 ng/dL ≤ μ ≤ 89 ng/dL and 152ng/dL ≤ μ ≤183ng/dL for the feminine and masculine sex individuals respectively

Validation of the Deardorff model for estimating energy balance components for a sugarcane crop

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of levomepromazine and different desflurane concentrations upon electrocardiographic variables in dogs

Objectives To investigate the effects of levomepromazine and different desflurane concentrations upon electrocardiographic variables.Animals Twenty adult mongrel dogs of both sexes weighing 6-28 kg.Methods Dogs were divided into two groups of 10 animals. Group I received 1 mg kg(-1) lV of levomepromazine and 15 minutes later anesthesia was induced with propofol (3 mg kg(-1) IV). Desflurane end-tidal concentration was set at 1.6 MAC. After 30 minutes at this concentration, measurements were taken and the end-tidal concentration was reduced to 1.4 MAC. Thereafter, it was reduced to 1.2 and then 1.0 MAC at 1.5-minute intervals. The same procedure was followed for group 2, except that levomepromazine was replaced with 0.2 mL kg(-1) of 0.9% saline solution and more propofol was needed for induction (7 mg kg(-1)). The animals' body temperature was maintained between 38.3 and 39 degreesC using a heating pad. The electrocardiographic tracing was obtained from lead II throughout the experimental period. The measurements were taken immediately before the administration of levomepromazine or placebo (T-1), 15 minutes after pre-medication (T-2) and 30 minutes after the establishment of 1.6 MAC (T-3)The other measurements were made at the concentrations of 1.4, 1.2, and 1.0 MAC, respectively (T4-6). The numerical data were submitted to analysis of variance plus F-test (p < 0.05).Results the dogs that received levomepromazine had a decrease in heart rate. However, in both groups it increased with desflurane administration. Levomepromazine, in association with desflurane, did not induce significant electrocardiographic changes, and all mean values (except P-wave duration) were within the reference range for this species.Conclusions and clinical relevance This study documented that levomepromazine, in association with desflurane, does not induce significant changes in electrocardiographic variables, suggesting that this drug combination has minimal effect on myocardial conduction.

Reference evapotranspiration estimation inside greenhouses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Selection and validation of reference genes for gene expression studies by reverse transcription quantitative PCR in Xanthomonas citri subsp citri during infection of Citrus sinensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)