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[Background] Antimicrobial resistance is a threat to global public health. The use of prolonged infusions in the hospital setting for certain antimicrobials is widely increasing in order to improve their efficacy and safety, including resistance development. Due to limited vascular access, it is important to clarify whether they can be infused through the same line with other drugs during Y-site administration., [Aim] The aim of this review is to update and summarize the evidence on Y-site compatibility of antibacterial agents administered as prolonged infusions in intensive care units (ICUs). Study Design A literature review of PubMed, EMBASE and Trissel's Handbook on Injectable Drugs databases was conducted on the compatibility of selected antimicrobials administered simultaneously at a Y-site connection with parenteral nutrition and other widely used drugs in ICUs. All articles published up to October 30, 2021, in English or Spanish were included, regardless of the type of publication (original articles, case reports, letters, etc.). Eligible antimicrobials were those that can be administered as prolonged infusions: ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ceftolozane/tazobactam, ceftaroline, cloxacillin, ceftobiprole, vancomycin and fosfomycin., [Results] A total of 1302 drug-to-drug potential combinations were explored, 196 (15.05%) were found to be incompatible, and in 541 (41.55%), data were not available. The results were presented in a simple 2-dimensional consultation chart as a quick reference for health care professionals., [Conclusions] This review provides useful and reliable information on the compatibility of antimicrobials administered as Y-site infusion with other drugs commonly used in the critical setting. This review contributes to patient safety in nursing practice. Relevance to Clinical Practice To our knowledge, this is the first review on Y-site compatibility of antimicrobials used as prolonged infusions with other commonly used drugs, including anti-emetics, analgesics and anti-epileptic and parenteral nutrition. The results of the current review need to be addressed to promote the knowledge sharing between health professionals and improve the quality and safety of patients. We believe that this review may serve as a simple and effective 2-dimensional updated drug-to-drug compatibility reference chart for critical care nurses.

Background: The trustworthiness of randomised clinical trials (RCTs) is suffering a crisis of confidence. Objectives: We undertook an umbrella review of the research integrity literature concerning RCTs. Search strategy and selection criteria: Following prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, Cochrane Library and Google Scholar, without language or time restrictions until November 2021. We included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle. Data collection and analysis: We assessed methodological quality using a modified AMSTAR-2 tool and collated the main findings. Main results: There were 55 relevant reviews summarising a total of 6001 studies (median per review 63; range 8-1106 studies). The overall quality of 53 (96.4%) reviews was critically low. Eight (14.6%) reviews focused on the general aspects of a RCT, 12 (21.8%) on the design and approval, 6 (10.9%) on the conduct and monitoring, 21 (38.2%) on the reporting of protocols and findings, one (1.8%) on post-publication concerns and 7 (12.7%) on future research and development. The integrity issues covered were varied, the most common being the importance of ethics (10/55, 18.2%) and transparency (10/55, 18.2%). Conclusions: Various research integrity issues covering RCT lifecycle, captured from mostly low-quality reviews, provided a broad overview emphasising the need for high level of ethical standards and professionalism. Many gaps in the RCT integrity landscape were also identified. There is a need to generate multistakeholder consensus to create specific RCT integrity standards.

Objectives To determine the β-lactam exposure associated with positive clinical outcomes for Gram-negative blood stream infection (BSI) in critically ill patients. Patients and methods Pooled data of critically ill patients with mono-microbial Gram-negative BSI treated with β-lactams were collected from two databases. Free minimum concentrations (fCmin) of aztreonam, cefepime, ceftazidime, ceftriaxone, piperacillin (co-administered with tazobactam) and meropenem were interpreted in relation to the measured MIC for targeted bacteria (fCmin/MIC). A positive clinical outcome was defined as completion of the treatment course or de-escalation, without other change of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation. Drug exposure breakpoints associated with positive clinical outcome were determined by classification and regression tree (CART) analysis. Results Data from 98 patients were included. Meropenem (46.9%) and piperacillin/tazobactam (36.7%) were the most commonly prescribed antibiotics. The most common pathogens were Escherichia coli (28.6%), Pseudomonas aeruginosa (19.4%) and Klebsiella pneumoniae (13.3%). In all patients, 87.8% and 71.4% achieved fCmin/MIC ≥1 and fCmin/MIC >5, respectively. Seventy-eight patients (79.6%) achieved positive clinical outcome. Two drug exposure breakpoints were identified: fCmin/MIC >1.3 for all β-lactams (predicted difference in positive outcome 84.5% versus 15.5%, P 4.95 for meropenem, aztreonam or ceftriaxone (predicted difference in positive outcome 97.7% versus 2.3%, P Conclusions A β-lactam fCmin/MIC >1.3 was a significant predictor of a positive clinical outcome in critically ill patients with Gram-negative BSI and could be considered an antibiotic dosing target.

Background Antimicrobial resistance has become a global challenge in healthcare and is usually associated with poor antibiotic-prescribing patterns. Purpose We sought to determine the rate and characteristics of antibiotic prescription in order to design future targeted antimicrobial stewardship interventions. Material and methods A point prevalence survey was carried out in the framework of the multi-centre study of international prevalence Global PPS 2017 (www.globalpps.com) in November 2017. The study was conducted from the analysis of all prescriptions of active antibiotics at 8 am at the hospital in a single day. A descriptive study (frequency and percentage) of the variables explored was carried out. Results Of 174 patients eligible for the study, quality indicators for antimicrobial prescriptions were: compliance with institutional guidelines: 100%, 62.3% and 57.8% (p There were therapeutic indications in 129 of the prescriptions, of which 22.5% were for skin and soft-tissue infections, followed by 15.5% complicated urinary tract infections and 9.3% pneumonia. Amoxicillin-clavulanate was the most prescribed antibiotic for treatment and prophylaxis purposes (48.1% and 29.8% respectively). According to syndrome, worst guideline compliance was observed in complicated urinary tract infections 57.9% and skin and soft-tissue infections (65.5%). Conclusion In our setting, adequate acquisition definition, compliance with local guidelines, obtaining of microbiological samples and certain clinical syndromes (skin and soft tissue and urinary) were the main variables identified to prioritise ASP-targeted intervention. References and/or acknowledgements No conflict of interest.

Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients. After exogenous administration, supra-physiological concentrations in serum are only ephemeral, which may explain the absence of significant therapeutic effect on sleep. The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aiming to simulate endogenous release.Thirteen patients in the recovery phase of critical illness were randomised to receive enteral melatonin or placebo. In the melatonin group, a total of 6 mg was administered as solution through their feeding tube, commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly. The placebo was administered using a similar regimen. Serial blood samples were taken and measured using a validated chromatographic method. The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling.The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients. The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients. The patients administered melatonin had a mean clearance, volume of distribution and absorption rate constant of melatonin was 55.2 L/h, 767 L and 0.76 hExogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight.

Un componente esencial de los sistemas agrícolas productivos es el riego, con el cual se logran los mejores resultados cuando su aplicación es eficiente y adecuada, de no ser así se puede afectar directamente los rendimientos y productividad del sistema (Banco Mundial, 2012). Cuando las características climáticas de una región muestran deficiencia en sus balances hídricos, como es el caso del área del Distrito de Riego del Triángulo del Tolima (DRTT), se requiere en lo posible de la implementación de sistemas de riego eficientes, teniendo en cuenta los cultivos y las características sociales de los agricultores. Dicho lo anterior se planteó este estudio, partiendo de la pregunta de investigación ¿Son adecuados los sistemas de riego presurizado en las parcelas demostrativas así como los diseños agrícolas propuestos para la zona del DRTT en el municipio de Natagaima - Tolima?, para encontrar solución a este interrogante se formuló el objetivo de “Evaluar la propuesta de riego presurizado establecido en cuatro parcelas demostrativas del DRTT, para generar alternativas bajo el enfoque agroecológico y el conocimiento local que permita optimizar la gestión del agua”.

Endarteriectomy is an operation originally proposed by Dos Santos in which a thrombus and the portion of the arterial wall to which it is attached are removed and the lumen of the artery re-established. The technic of this operation is described. Case histories of several patients illustrating the results which the authors have obtained are presented.

Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic 'real-practice' trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry.