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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing.FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms.INTERPRETATION: Patient's age, timing of cannulation (FUNDING: None.

Tumors with microsatellite instability (MSI) are caused by a defective DNA mismatch repair system that leads to the accumulation of mutations within microsatellite regions. Indels in microsatellites of coding genes can result in the synthesis of frameshift peptides (FSP). FSPs are tumor-specific neoantigens shared across patients with MSI. In this study, we developed a neoantigen-based vaccine for the treatment of MSI tumors. Genetic sequences from 320 MSI tumor biopsies and matched healthy tissues in The Cancer Genome Atlas database were analyzed to select shared FSPs. Two hundred nine FSPs were selected and cloned into nonhuman Great Ape Adenoviral and Modified Vaccinia Ankara vectors to generate a viral-vectored vaccine, referred to as Nous-209. Sequencing tumor biopsies of 20 independent patients with MSI colorectal cancer revealed that a median number of 31 FSPs out of the 209 encoded by the vaccine was detected both in DNA and mRNA extracted from each tumor biopsy. A relevant number of peptides encoded by the vaccine were predicted to bind patient HLA haplotypes. Vaccine immunogenicity was demonstrated in mice with potent and broad induction of FSP-specific CD8 and CD4 T-cell responses. Moreover, a vaccine-encoded FSP was processed in vitro by human antigen-presenting cells and was subsequently able to activate human CD8 T cells. Nous-209 is an “off-the-shelf” cancer vaccine encoding many neoantigens shared across sporadic and hereditary MSI tumors. These results indicate that Nous-209 can induce the optimal breadth of immune responses that might achieve clinical benefit to treat and prevent MSI tumors.Significance:These findings demonstrate the feasibility of an “off-the-shelf” vaccine for treatment and prevention of tumors harboring frameshift mutations and neoantigenic peptides as a result of microsatellite instability.

List of 1087 FSPs suitable for the inclusion in NOUS-209 vaccine.

Effective treatment approaches for biofilms in endotracheal tubes (ETTs) are lacking. In this study, we evaluated the in vitro effects of five antimicrobials against biofilms formed by Klebsiella pneumoniae in ETTs. K. pneumoniae was added to minimal mucin medium prior to inoculation in microtiter plates containing ETT fragments. Biofilm susceptibility was assessed by crystal violet staining. At 24 h, the antimicrobials significantly reduced biofilm formation. At 48 h, all of the antimicrobial agents exhibited significant reductions in biofilm formation, even at concentrations above the minimum inhibitory concentration (MIC). Tigecycline and fosfomycin showed the greatest inhibition capacity, with good activity at concentrations twofold greater than the MIC. K. pneumoniae exhibited excellent biofilm formation ability, with formation in the first 24 h and significantly reduced antimicrobial activity. These results contribute to the establishment of new antibiotic breakpoints for the adequate management of infections associated with biofilm formation. Abbreviations ETT Endotracheal tube MIC Minimum inhibitory concentration MBIC Minimum biofilm inhibitory concentration OD Optical density PBS Phosphate-buffered saline VAP Ventilator-associated pneumonia.

Objective Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. Design Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. Setting 36-bed MCCU in referral tertiary hospital. Patients and participants SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. Interventions None Main variables of interest Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Results Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 – 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. Conclusions The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.

This survey addressed a twofold need: first, research into speech sound productions in children with visual impairments and, second, evidence upon which speech-language pathologists might base interventions for children with visual impairments. Fifteen speech-language pathologists responded to a survey about speech sound productions in caseload children with visual impairments. Respondents reported the speech characteristics of 46 children, their coexisting medical diagnoses and developmental conditions, the nature of their visual impairments, and therapy approaches used. Children and teens with visual impairments demonstrated speech sound production errors. It is not conclusive that errors resulted from having visual impairments. Respondents reported effective speech treatment techniques. This study contributes a detailed report of speech sound productions in children who, despite a diversity of coexisting diagnoses, had visual impairment in common. Findings provide a point of reference regarding speech sound productions in children with visual impairments, as well as efficacious treatments.

Background: Health-care associated infections are a major cause of morbidity and mortality in critical care units. The aim of this study is to evaluate the effectiveness of chlorhexidine gluconate (CHG)-impregnated wipes in the daily bathing of patients in an intensive care unit (ICU) to prevent cross-transmission and colonization by multidrug-resistant organisms (MDROs) Methods: Prospective cohort study with an intervention of 11 months. The intervention consisted of using CHG-impregnated wipes for the daily bathing of patients on mechanical ventilation or colonized by MDROs. Monthly trends in the number of patients colonized by MDROs and the incidence of nosocomial infections were evaluated. Results: A total of 1,675 patients were admitted to the unit during the intervention period, and 430 (25.7%) were bathed with chlorhexidine wipes. A significant decrease was observed in the incidence of colonization by MDROs over the months (beta = -0.209; r(2) = 0.549; P = .027), and in the number of patients colonized compared with the equivalent period of the previous year (22.0% vs 18.4%; P = .01). No significant decrease was observed in the incidence of nosocomial infection between the two periods (4.11% vs 4.57%; P = .355). No dermatologic problems were observed in the treated patients. Conclusions: The use of CHG-impregnated wipes reduces cross-transmission and colonization by MDROs in the ICUs in an endemic situation because of multidrug-resistant Enterobacteriaceae. (C) 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

This study documented the communicative behaviors exhibited by sibling dyads comprised of one typically developing child and his/her sibling with autism. Six US families participated in one 45-minute home observation of sibling interactions, a 20-minute semi-structured interview with the typically developing child, and a 20-minute semi-structured interview with the siblings’ parents. Dyads varied across birth order, ages, and genders. Observational data were coded to reveal 38 categories of communicative behaviors and their frequency of occurrence. Interviews yielded information about the siblings’ usual interactions and parents’ perceptions about their children’s relationships. Families provided evidence of sibling support for the communication skills of the child with autism. Findings have implications for siblingmediated facilitation of communicative behaviors in children with autism.

Recent advances in next generation sequencing expanded the availability of tumor mutanome data that list the mutations present in cancer cells. Mutated proteins are an interesting source of neoantigens that can be used to specifically target tumor cells in the context of immunotherapy. However, identifying new antigenic peptides from mutated proteins remains challenging. In this chapter, we present Reverse Immunology as an approach to identify potential antigens from any given polypeptide sequence. First, we explain the rationale behind the identification of candidate HLA-binding peptides through mass spectrometry or in silico approaches. Then, we describe the isolation of low-frequency T-cell precursors specific for the candidate peptides using peptide-HLA multimers. Finally, we discuss validation steps leading to the identification of a T-cell clone recognizing tumor cells that endogenously process the candidate peptide. We also present approaches to study the impact of the proteasome complex on candidate peptide processing.

Objectives To assess tolvaptan's efficacy and safety in critical care patients with volume overload. Methods Prospective observational study. Twenty-eight patients in the recovery phase from multiple organ failure and with volume overload refractory to conventional therapy treated with tolvaptan were included. Results Patients received an initial daily dose of 3.75 (n=1), 7.5 (n=8) and 15 (n=19) mg of tolvaptan. Median treatment duration was 2 days (range: 1 to 12). All patients presented an increase in 24 hours diuresis after the first dose (median increase from baseline (IQR)=1114 (285-1943) mL), with a median net daily fluid loss of 1007 mL (456-2380) mL after 24 hours. High diuretic efficacy (daily fluid loss higher than 0.5 L with tolvaptan first dose) was detected in 18 patients (64.3%). Initial hyponatraemia was present in 16 (57.1%) patients, while overly rapid correction with tolvaptan treatment occurred in two patients without clinical consequences. Two patients presented hypophosphataemia after treatment. Conclusion Tolvaptan is an effective therapeutic option in critically ill patients with volume overload refractory to conventional diuretics. Further studies are required to evaluate its safety profile and its effect on short-term outcomes and mortality.

In this study, we evaluate the effect of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (Levitronix) on the pharmacokinetic of amikacin in critically ill patients. Twelve patients with ECMO and three with Levitronix devices who started treatment with amikacin were included. Amikacin pre (Cmax) and post (Cmin) dose serum concentrations were measured during the first 72-96 hours of treatment initiation. Pharmacokinetic parameters were performed by Bayesian adjustment. The median initial dose was 1,000 mg (range: 600-1,400 mg). Mean plasma concentrations were Cmax 58.6 mg/L (17.0 mg/L); Cmin 9.58 mg/L (7.8 mg/L). Patients with an ECMO device had a higher volume of distribution (0.346 [0.033] vs. 0.288 [0.110] L/kg) and a lower plasma clearance (1.58 [0.21] vs. 3.73 [1.03] L/h) than the control group. This phenomenon was also observed in those patients with simultaneous use of ECMO and hemodilafiltration. For patients with Levitronix system, no significant alterations in the volume of distribution were observed, although a lower plasma clearance was noticed. Placement of ECMO devices alters the pharmacokinetic parameters of amikacin in the critically ill patients and should be considered when selecting the initial dose.

Background Continuous renal replacement therapy (CRRT) is common practice in critical care patients with acute renal failure. Objectives To evaluate the adequacy of antimicrobial doses calculated based on the total drug clearance and dose recommended by different guides in critically ill patients undergoing CRRT. Methods Retrospective observational study. Patients admitted to a critical care unit during May 2014 to May 2016 and subjected to CRRT were included. The recommended dose was established as the product of the usual dose of the drug by total drug clearance. Results 177 antimicrobial agents, used in 64 patients were analysed; 45 (25.4%) antimicrobials were given in an insufficient dose (

This quantitative cross-sectional comparative study used the National Institute for Occupational Safety and Health occupational stress model to determine if stress levels and associated health outcomes vary among university educators based on work environment. Occupational stress has been identified as the most damaging form of stress, leading to lost work hours, low productivity, numerous health issues, and high health care costs. This study used a survey of 1,000 university instructors within the United States comparing undergraduate online educators who work remotely, undergraduate educators who work in an on-ground university, and undergraduate educators in a mixed environment. There was a significant difference in self-reported stress levels across groups, with on-ground educators experiencing more stress than online educators. No significant difference existed in health outcomes across groups.

Resumen Objetivo Analizar la utilidad de la procalcitonina (PCT) para el diagnostico de infeccion en pacientes con cirrosis hepatica ingresados en una unidad de cuidados intensivos. Diseno Estudio observacional retrospectivo. Ambito Unidad de Cuidados intensivos. Polivalente, 24 camas. Participantes Pacientes con cirrosis hepatica ingresados en nuestra unidad de cuidados intensivos en los ultimos 4 anos con diagnostico de sospecha de infeccion y determinacion de PCT. Resultados Entre los 255 pacientes con cirrosis ingresados en nuestra unidad; se determino la PCT para el diagnostico diferencial de infeccion en 69 casos (27%). Tres pacientes fueron excluidos del analisis por falta de datos clinicos. La estancia media fue de 10,6 ± 9,2 dias y la mortalidad del 65%. El origen de la cirrosis fue virico (57%) o enolico (37%), con una puntuacion de 9,5 ± 2 en la escala de Child-Pugh y 23 ± 8 en la escala de MELD. En 54 pacientes (82%) se establecio el diagnostico de infeccion. La infeccion mas frecuente fue la neumonia (72%), seguida de la infeccion intraabdominal (18%), y la bacteriemia (5%). En los pacientes sin infeccion la mediana de PCT fue de 0,57 ng/ml (0,28-1,14) frente a 2,99 (1,31-9,4) p Conclusiones En los pacientes con cirrosis hepatica la PCT es util para identificar la presencia de infecciones bacterianas incluyendo las intraabdominales.

Objective To evaluate the usefulness of procalcitonin (PCT) for diagnosing infection in patients with liver cirrhosis admitted to an Intensive Care Unit. Design A retrospective study was carried out. Scope Intensive Care Unit. Versatile, twenty-four beds. Participants Patients with liver cirrhosis admitted to our Intensive Care Unit in the last 4 years with suspected infection and measurement of PCT. Results Among the 255 patients with cirrhosis admitted to our unit, PCT was determined for the differential diagnosis of infection in 69 cases (27%). Three patients were excluded from analysis due to a lack of clinical data. The average stay was 10.6 ± 9.2 days, with a mortality rate of 65%. The origin of cirrhosis was mainly viral (57%) or alcoholic (37%). The Child–Pugh and MELD scores were 9.5 ± 2 and 23 ± 8, respectively. Infection was diagnosed in 54 patients (82%). The most common infection was pneumonia (72%), followed by intraabdominal infections (18%) and bacteremia (5%). In patients without infection, the median PCT concentration was 0.57 ng/ml (range 0.28–1.14) versus 2.99 (1.31–9.4) in those with infection (p Conclusions In patients with liver cirrhosis, PCT is useful for identifying bacterial infections, including intraabdominal processes.

Background The aim of this study is to evaluate the risk factors for colonisation by multidrug resistant (MDR) K. pneumoniae in a critical care unit and the relationship between colonisation and the antibiotic pressure exerted by the antimicrobial treatments received by patients. Methods A prospective observational was designed. Patients admitted for more than 48 h to an intensive care unit were included. Samples for surveillance cultures were obtained from all the patients upon admission and once a week. The association between risk factors and colonisation by MDR K. pneumoniae was determined by logistic regression. A Cox regression model was used to evaluate the effect of the use of antimicrobials on the colonisation rate. An ARMIA model was used to investigate the association between the incidence of colonisation by MDR strains and the global consumption of antimicrobials in the unit. Results One thousand seven hundred twenty-five patients were included, from which 308 (17.9%) were positive for MDR K. pneumoniae. In the multivariate analysis, hospitalisation for longer than 7 days together with respiratory infection and administration of any antibiotic was associated with increased MR K. pneumoniae colonisation. Patients who received antibiotics for more than 48 h were colonised earlier than patients who did not receive antibiotic treatment [HR: 2.16 (95%CI:1.55–3.03)]. The ARIMA model found a significant association between the monthly colonisation rate for MR K. pneumoniae and the consumption of cephalosporins and carbapenems in the previous month. Conclusion Individual antibiotic administration and the global antibiotic pressure of cephalosporins and carbapenems are associated to an increased colonisation by MDR K. pneumoniae strains.

What is known and objective Several authors have demonstrated the relationship between voriconazole concentrations and the risk of therapeutic failure and adverse events However, the information about voriconazole concentrations in the critically ill patient is scarce. The aim of this study was to analyse the plasma concentrations and pharmacokinetic behaviour of voriconazole in critically ill patients and their association with the treatment response and development of toxicity. Methods A prospective, observational study was conducted. Patients admitted to an intensive care unit and on treatment with intravenous voriconazole were included. Plasma concentrations were measured between days 4 and 7 from the start of the treatment. The pharmacokinetic analysis was performed using the NONMEM® software. A regression model was used to evaluate the variables associated with the values outside the therapeutic range, as well as the relationship between the plasma concentrations and the treatment response and the development of hepatotoxicity. Results and discussion A total of 33 patients were included. Plasma concentrations outside the therapeutic range (1-5.5 mg/L) were observed in 15 patients, being above the established range in 9 (27.3%) cases, and below it in 6 (18.2%) cases. The presence of a bilirubin value of >1.5 mg/dL and a C-reactive protein >100 mg/dL was associated with supra-therapeutic concentrations. Voriconazole concentrations greater than 5.5 mg/dL were associated with the development of hepatotoxicity. What is new and conclusions There is a wide variation in voriconazole concentrations in critically ill patients, being associated with a high frequency of adverse events. Close monitoring of these values is required in order to decrease the risk of therapeutic failure and toxicity.

Purpose Information about immunocompromised patients infected with influenza A (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to know the clinical characteristics of these patients and to identify treatment-related variables associated with mortality. Material and methods A prospective multicenter observational cohort study was based on data from a Spanish registry (2009–2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with the diagnosis of influenza A (H1N1) virus infection were included. Immunosuppression was clearly defined. Factors associated with mortality in immunocompromised patients were assessed by conventional logistic regression analysis and by a propensity score (PS) adjusted-multivariable analysis. Results Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified as immunocompromised. Mortality was significantly higher in immunosuppressed patients. Four variables independently associated with mortality were identified: SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure, AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an independent factor associated with increased mortality (OR 2.25;95%CI, 1.15–4.38;p = 0.017). In the subgroup of hematological patients (n = 141), corticosteroid therapy was also associated with increased mortality (OR 3.12; 95%CI, 1.32–7.41; p = 0.010). Conclusion Immunocompromised individuals with influenza A (H1N1) admitted to the ICU have a poor outcome. In this population, the use of corticosteroids is strongly discouraged.

Objectives: The aim of this study was to determine the persistence of the adverse prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting with low vancomycin use. Methods: A retrospective study focusing on episodes of bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was designed. The main outcome measures were 30-day mortality and treatment failure. Multivariate logistic regression analysis was used to identify variables associated with patient mortality and treatment outcome. Results: In total, 79 MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0 mu g/mL in 53 episodes (67.1%). The presence of high vancomycin MIC was not associated with a higher mortality rate or treatment success. A daptomycin MIC >= 0.5 mu g/mL was present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained and was associated with 30-day mortality in the multivariate analysis (odds ratio = 4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used were associated with a lower risk of treatment failure or mortality. Conclusions: The pernicious effect of high vancomycin MIC disappears in the absence of a predominant use of this antibiotic. However, a high daptomycin MIC in MRSA bacteraemia is associated with higher mortality in patients with bacteraemia, irrespective of antimicrobial treatment choice. (C) 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Objective: The objective of this study was to evaluate the impact of the empirical therapy with fluconazole or an echinocandin on 30- and 90-day mortality in critically ill patients with candidemia. The outcome of patients in whom the empirical echinocandin was deescalated to fluconazole was also assessed. Design: Retrospective, observational multicenter study. Setting: Medical and surgical ICUs in nine Spanish hospitals. Patients: Adult patients ( 18 yr) with an episode of Candida bloodstream infection during ICU admission from January 2011 to April 2016. Interventions: Patient characteristics, infection-related variables, therapeutic interventions, and metastatic complications were reviewed. A propensity score-adjusted multivariable analysis was performed to identify the risk factors significantly associated with 30-day and 90-day mortality. Measurements and Main Results: A total of 294 patients were diagnosed of candidemia in the participant ICUs. Sixty patients were excluded (other antifungals in the primary therapy or the patient died without empirical antifungal therapy). The study group comprised 115 patients who received fluconazole (30-day mortality, 37.4%) and 119 patients treated empirically with an echinocandin (30-day mortality, 31.9%). The use of an echinocandin in the empirical therapy was a protective factor for 30-day (odds ratio, 0.32; 95% CI, 0.16-0.66; p = 0.002) and 90-day mortality (odds ratio, 0.50; 95% CI, 0.27-0.93; p = 0.014) in the propensity score- adjusted multivariable analysis. Deescalation of the empirical echinocandin to fluconazole was not associated with a higher mortality or the occurrence of long-term complications. Conclusions: Empirical use of an echinocandin in critically ill patients with documented candidemia reduces mortality at 30 and 90 days significantly. Deescalation of the empirical echinocandin to fluconazole is safe and effective in fluconazole-susceptible infections.

Objective: Hospital antimicrobial stewardship programmes have achieved savings and a more rational use of antimicrobial treatments in general wards. The purpose of this report is to evaluate the experience of an antimicrobial stewardship programme in an intensive care unit (ICU). Design: Prospective interventional, before-and-after study. Scope: 24-bed medical ICU in a tertiary hospital. Intervention: Prospective audit and feedback antimicrobial stewardship programme. Endpoints: Antimicrobial consumption, antimicrobial related costs, multi-drug resistant microorganisms (MDRM) prevalence, nosocomial infections incidence, ICU length of stay, and ICU mortality rates were compared before and after one-year intervention. Results: A total of 218 antimicrobial episodes of 182 patients were evaluated in 61 team meetings. Antimicrobial stewardship suggestions were accepted in 91.5% of the cases. Total antimicrobial DDD/100 patient-days consumption was reduced from 380.6 to 295.2 (-22.4%; p = 0.037). Antimicrobial stewardship programme was associated with a significant decrease in the prescription of penicillins plus b-lactamase inhibitors, linezolid, cephalosporins, and aminoglycosides. Overall antimicrobial spending was reduced by (sic) 119,636. MDRM isolation and nosocomial infections per 100 patient-days did not change after the intervention period. No changes in length of stay or mortality rate were observed. Conclusions: An ICU antimicrobial stewardship programme significantly reduced antimicrobial use without affecting inpatient mortality and length of stay. Our results further support the implementation of an antimicrobial stewardship programme in critical care units. (C) 2017 Elsevier Espana, S.L.U. y SEMICYUC. All rights reserved.

Background: To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations. Methods: Prospective observational study. Patients receiving CVVHDF and amikacin treatment were included. Pharmacokinetic parameters were calculated using Bayesian analysis. Spearman correlation test was used in order to assess the influence of CVVHDF flux on amikacin minimum concentration (Cmin) and plasma clearance. Results: Thirty patients undergoing CVVHDF procedures were included. The treatment with amikacin started at an initial mean dose of 12.4 (4.1) mg/kg/day. An association between the flow rate and Cmin value (r = 0.261; p = 0.161) and plasma clearance was found (r = 0.268; p = 0.152). Four patients (13.3%) were not able to achieve peak concentration over MIC value higher than 8. In 4 patients, amikacin had to be discontinued due to a high Cmin value. Conclusions: Amikacin clearance in patients with CVVHDF is affected by the flow rate used. Therefore, CVVHDF dose should be taken into account when dosing amikacin.

Introduction: The information about the pharmacokinetics and optimal dose of tigecycline in critically ill patients with severe underlying diseases is limited and controversial. In this study, we evaluate the pharmacokinetic parameters of tigecycline in critically ill patients with multidrug-resistant Gram-negative infection and explore the association between the pharmacokinetic/pharmacodynamic ratio and treatment response. Methods: A prospective study was designed including critically ill patients treated with tigecycline for multidrug-resistant Gram-negative infections. Blood samples were collected at day 3–5 of treatment, and pharmacokinetics parameters were evaluated using NONMEM® software. Relationship between area under the free concentration–time curve and minimum inhibitory concentration ratio (fAUC/MIC) and treatment failure was evaluated. Association between tigecycline fAUC and hepatobiliary toxicity was also investigated. Results: Twenty-five critically ill patients were included in the study. In the pharmacokinetic model, weight and total bilirubin level were found to be significant predictors of tigecycline clearance. Fifteen (60.0%) patients achieved an fAUC/MIC ratio >4.5, seven (28.0%) an fAUC/MIC > 6.96 and only three (12.0%) an fAUC/MIC > 17.9. No differences in fAUC/MIC ratio were obtained between those patients with and without clinical failure (5.28 (IC95%: 2.57–7.94) vs 8.71 (3.57–13.84)). fAUC values were higher in those patients who suffered hepatobiliary disorders (7.63 (3.93–11.34) vs 17.63 (7.85–26.28) mg/L/h). Conclusion: An important percentage of critically ill patients with multidrug-resistant Gram-negative infection treated with tigecycline do not achieve an appropriate pharmacokinetic/pharmacodynamic value. Tigecycline fAUC seems to be associated with hepatobiliary disorders in this study population. The effect of fAUC/MIC ratio on clinical response remains unclear.

What is known and objective Positive volume balance is related with high mortality in critically ill patients. We describe our experience in the use of tolvaptan in patients with fluid overload. Case summary Six patients in the recovery phase from septic shock were included. All patients achieved an increase in diuresis after the first day, with a median fluid balance variation of −2362 (−485 to −3447) mL. At the end of treatment, median fluid balance variation was −9080 (−26 784 to −4395) mL. What is new and Conclusion Tolvaptan could be an option in critically ill patients with fluid overload and resistant or not treatable with conventional diuretics.

This article describes the application of adult experiential learning theory to the clinical supervision of graduate student clinicians in communication sciences and disorders. The proposed adult experiential learning model integrates enhanced and updated interpretations of Bloom’s Taxonomy. Practical tools to help supervisors and supervisees implement the model are provided: a clinical supervision worksheet and two case studies illustrating use of the model.

Adult learning models rarely are applied to clinical supervision in communication sciences and disorders. Little evidence exists to attest to the utility of implementing adult learning models durin...

The purpose of this study was to assess the effectiveness of silver-embedded surfaces (BactiBlockA (R)) to prevent surface colonization by multi-resistant bacteria (MRB) and to reduce the incidence of MRB colonization and infection in patients admitted to an intensive care unit (ICU). A 6-month prospective observational study in a 24-bed mixed ICU divided into two identical subunits (12 beds each) was designed. Seven solid mobile screens were placed in one of the subunits while in the other cloth screens remained. Solid screens were constructed with high-density polyethylene embedded in BactiblockA (R). To evaluate the effectiveness of screens coated with BactiblockA (R), number of MRB isolates on screens were compared for 6 months. Likewise, numbers of new patients and ICU-stays with MRB colonization in the two subunits were compared. One hundred forty screen samples were collected in 10-point prevalent days. MRB were detected on 28 (20.0%) samples. Over the 70 samples taken on cloth folding screens, MRB were detected in 25 (35.7%), while only 3 (4.3%) of the 70 samples taken on BactiblockA (R) screens were positive for MRB (p < 0.001). The unit with BactiblockA (R) screens presented fewer number of ICU stays with MRB colonization (27.8% vs 47.1%; p < 0.001). No significant differences were found in the global incidence of MRB nosocomial infection. The presence of BactiblockA (R) embedded in solid folding screens avoided MRB surface colonization and reduced MRB transmission to patients admitted to critical care units, proving to be an useful tool in the control of MRB.