Extracting probability in the absence of visual awareness.

Extracting statistical regularities from the environment is crucial for survival. It allows us to learn cues for where and when future events will occur. Can we learn these associations even when the cues are not consciously perceived? Can these unconscious processes integrate information over long periods of time? We show that human visual system can track the probability of location contingency between an unconscious prime and a conscious target over a period of time of minutes. In a series of psychophysical experiments, we adopted an exogenous priming paradigm and manipulated the location contingency between a masked prime and a visible target (i.e., how likely the prime location predicted the target location). The prime's invisibility was verified both subjectively and objectively. Although the participants were unaware of both the existence of the prime and the prime-target contingency, our results showed that the probability of location contingency was tracked and manifested in the subsequent priming effect. When participants were first entrained into the fully predictive prime-target probability, they exhibited faster responses to the more predictive location. On the contrary, when no contingency existed between the prime and target initially, participants later showed faster responses to the less predictive location. These results were replicated in two more experiments with increased statistical power and a fine-grained delineation of prime awareness. Together, we report that the human visual system is capable of tracking unconscious probability over a period of time, demonstrating how implicit and uncertain regularity guides behavior.

An international survey on aminoglycoside practices in critically ill patients: the AMINO III study.

BACKGROUND: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock. RESULTS: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of Cmax and Cmin was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a Cmax/MIC > 8 and 353 (71%) having concentrations above Cmin recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes. CONCLUSION: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Consenso de farmacia clínica intensiva a nivel nacional / Consensus about the duties of pharmacists in intensive care units in Chile

In 2015, the directors of the Clinical Pharmacists Division of the Chilean Society of Intensive Care Medicine (SOCHIMI) organized a collaborative work along the country to define the minimum activities and duties that a pharmacist should perform in an Intensive Care Unit in Chile, according to the Ministry of Health and SOCHIMI guidelines and recommendations. This document summarizes the agreements on three priority areas of pharmacists' duties in intensive care: a) pharmacotherapy follow-up; b) pharmacological surveillance and security management of medications, and c) data recording and documentation. The recommendations collect the experiences from Chilean pharmacists along the country and provide information and support for future consensus for other specialties.

[Consensus about the duties of pharmacists in intensive care units in Chile]. / Consenso de farmacia clínica intensiva a nivel nacional.

In 2015, the directors of the Clinical Pharmacists Division of the Chilean Society of Intensive Care Medicine (SOCHIMI) organized a collaborative work along the country to define the minimum activities and duties that a pharmacist should perform in an Intensive Care Unit in Chile, according to the Ministry of Health and SOCHIMI guidelines and recommendations. This document summarizes the agreements on three priority areas of pharmacists' duties in intensive care: a) pharmacotherapy follow-up; b) pharmacological surveillance and security management of medications, and c) data recording and documentation. The recommendations collect the experiences from Chilean pharmacists along the country and provide information and support for future consensus for other specialties.

Liquid extracorporeal carbon dioxide removal: use of THAM (tris-hydroxymethyl aminomethane) coupled to hemofiltration to control hypercapnic acidosis in a porcine model of protective mechanical ventilation.

A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol·kg(-1)·h(-1) coupled to hemofiltration (THAM+HF group) at 100 mL·kg(-1)·h(-1). After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm·kg H2O(-1) at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis.

Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration.

This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V(1)), 11.8L; volume of distribution of peripheral compartment (V(2)), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.

Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.

PURPOSE: Medication errors (MEs) are a major factor limiting the effectiveness and safety of pharmacological therapies in critically ill patients. The purpose was to determine if a preventive interventions program (PIP) is associated with a significant reduction on prevalence of patients with MEs in intensive care unit (ICU). METHODS: A prospective before-after study was conducted in a random sample of adult patients in a medical-surgical ICU. Between 2 observational phases, a PIP (bundle of interventions to reduce MEs) was implemented by a multidisciplinary team. Direct observation was used to detect MEs at baseline and postintervention. Each medication process, that is, prescription, transcription, dispensing, preparation, and administration, was compared with what the prescriber ordered; if there was a difference, the error was described and categorized. Medication errors were defined according to the National Coordinating Council for Medication Error Reporting and Prevention. RESULTS: A total of 410 medications for 278 patients were evaluated. A 31.7% decrease on the prevalence of patients with MEs (41.9%-28.6%; P < .05) was seen. Main variations occurred in anti-infectives for systemic use and prescription and administration stage. CONCLUSIONS: The implementation of PIP by a multidisciplinary team resulted in a significant reduction on the prevalence of patients with ME at an adult ICU.

Consideraciones farmacocinéticas en el paciente crítico / Pharmacokinetic considerations in critically ill patients

Background: Critically ill patients in Intensive Care Units (ICUs) are exposed to multiple procedures and usually require complex treatment regimens. Many of them suffer from comorbidities and different complications such as organ failure, drug-drug interactions, and unusual therapeutic interventions that can produce significant pathophysiologic changes. For that reason, pharmacokinetics for several substances is different to what is described for healthy patients, complicating drug selection and drug dosage to achieve appropriate effects. Low doses may determine a reduction of drug effectiveness and overdoses leading to toxicity. The aim of this paper is to review the pharmacokinetic considerations that must be considered when treating acute ICU patients.

[Pharmacokinetic considerations in critically ill patients]. / Consideraciones farmacocinéticas en el paciente crítico.

Critically ill patients in Intensive Care Units (ICUs) are exposed to multiple procedures and usually require complex treatment regimens. Many of them suffer from comorbidities and different complications such as organ failure, drug-drug interactions, and unusual therapeutic interventions that can produce significant pathophysiologic changes. For that reason, pharmacokinetics for several substances is different to what is described for healthy patients, complicating drug selection and drug dosage to achieve appropriate effects. Low doses may determine a reduction of drug effectiveness and overdoses leading to toxicity. The aim of this paper is to review the pharmacokinetic considerations that must be considered when treating acute ICU patients.

Impacto del cuidado multidisciplinario en los desenlaces clínicos de los pacientes críticos / Impact of multidisciplinary teams on clinical outcomes of critically ill patients

La seguridad de los pacientes críticos en la Unidad de Cuidados Intensivos (UCI), ha sido progresivamente reconocida como un componente esencial de la práctica de la medicina intensiva moderna. La creación y promoción de equipos multidisciplinarios liderados por un intensivista ha demostrado mejorar la seguridad de la atención de salud. La incorporación de un farmacéutico con entrenamiento especializado a la UCI, ha generado un impacto positivo en los desenlaces clínicos y económicos. El fomento de la cultura de la seguridad en la UCI y el rediseño de los procesos defectuosos pueden mejorar significativamente la seguridad y calidad de la atención de los pacientes críticos.

The safety of critically ill patients in Intensive Care Unit (ICU) has been increasingly recognized as an essential component of the practice of modern intensive care. The creation and promotion of intensivist-led multidisciplinary teams has shown to improve the safety of health care. The addition in the ICU of a pharmacist with specialized training has generated a positive impact on clinical and economic outcomes. The promotion of safety culture in the ICU and the redesign of faulty processes can significantly improve the safety and quality of care of critically ill patients.

[Factors associated with non-compliance with antidepressant treatment in Santiago, Chile]. / Factores asociados al incumplimiento de los tratamientos con antidepresivos en Santiago, Chile.

OBJECTIVE: To identify factors associated with non-compliance to antidepressant's (AD) treatment in Santiago, Chile. METHODS: A cross-sectional study was carried out in a household randomized and representative sample of 1000 individuals aged 15 years and older. Treatment adherence was studied in AD consumers using logistic regression to estimate factors associated with non-compliance in doses or time of treatment. RESULTS: Antidepressant non-compliance was 52.8% and their main associated factor was income. Gender and educational level were also associated with AD non-compliance. CONCLUSIONS: Antidepressant non-compliance was associated with income and sociodemographic characteristics in Chilean patients. Therefore, health strategies to improve AD compliance should consider inequities in access to medications and characteristics of the AD consumers.