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Background: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. Methods: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. Results: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. Conclusions: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.). [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that levosimendan administration in patients with low cardiac output syndrome after cardiac surgery is associated with improved long-term (5-year follow-up) outcomes., Design: Single-center subanalysis of the multicenter randomized CHEETAH trial., Setting: Cardiac surgery department of a tertiary hospital., Participants: A total of 134 adult patients requiring hemodynamic support for a cardiac index <2.5 L/min/m 2 after cardiac surgery with cardiopulmonary bypass (CPB)., Interventions: Patients were randomized (1:1 ratio) to receive levosimendan (continuous infusion with a starting dose of 0.05 μg/kg/min) or placebo, in addition to standard inotropic care., Measurements and Main Results: The primary endpoint was long-term mortality (1-5 years) after randomization. Secondary outcomes were hemodynamic parameters, need for inotropic support, acute kidney injury (AKI), need for renal replacement therapy, duration of mechanical ventilation, intensive care unit (ICU) and hospital stay, and 30-day mortality. No significant between-group difference in long-term mortality (5 years) was observed (hazard ratio, 1.59; 95% confidence interval, 0.81 to 3.11; p = 0.17). There were no significant differences in secondary outcomes, except for the difference in the mean pulmonary artery pressure at 4 to 6 hours after randomization, which was lower in the levosimendan group compared to the placebo group (median, 24 [interquartile range (IQR), 21.8-28] mmHg vs 26 [IQR, 22.2-33] mmHg; p = 0.019)., Conclusions: Among patients requiring hemodynamic support after cardiac surgery with CPB, perioperative levosimendan infusion did not affect long-term survival (1-5 years) compared with placebo. Levosimendan also had no effect on major clinical outcomes such as AKI, ICU stay, hospital stay, and 30-day mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The healthcare sector poses many strategic, tactic and operational planning questions. Due to the historically grown structures, planning is often locally confined and much optimization potential is foregone., Methods: We implemented optimized decision-support systems for ambulatory care for four different real-world case studies that cover a variety of aspects in terms of planning scope and decision support tools. All are based on interactive cartographic representations and are being developed in cooperation with domain experts. The planning problems that we present are the problem of positioning centers for vaccination against Covid-19 (strategical) and emergency doctors (strategical/tactical), the out-of-hours pharmacy planning problem (tactical), and the route planning of patient transport services (operational). For each problem, we describe the planning question, give an overview of the mathematical model and present the implemented decision support application., Results: Mathematical optimization can be used to model and solve these planning problems. However, in order to convince decision-makers of an alternative solution structure, mathematical solutions must be comprehensible and tangible. Appealing and interactive decision-support tools can be used in practice to convince public health experts of the benefits of an alternative solution. The more strategic the problem and the less sensitive the data, the easier it is to put a tool into practice., Conclusions: Exploring solutions interactively is rarely supported in existing planning tools. However, in order to bring new innovative tools into productive use, many hurdles must be overcome., (© 2022. The Author(s).)

Primary care systems are a cornerstone of universally accessible health care. The planning, analysis, and adaptation of primary care systems is a highly non-trivial problem due to the systems' inherent complexity, unforeseen future events, and scarcity of data. To support the search for solutions, this paper introduces the hybrid agent-based simulation model SiM-Care. SiM-Care models and tracks the micro-interactions of patients and primary care physicians on an individual level. At the same time, it models the progression of time via the discrete-event paradigm. Thereby, it enables modelers to analyze multiple key indicators such as patient waiting times and physician utilization to assess and compare primary care systems. Moreover, SiM-Care can evaluate changes in the infrastructure, patient behavior, and service design. To showcase SiM-Care and its validation through expert input and empirical data, we present a case study for a primary care system in Germany. Specifically, we study the immanent implications of demographic change on rural primary care and investigate the effects of an aging population and a decrease in the number of physicians, as well as their combined effects., (© 2021. The Author(s).)

Objective: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention., Methods: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group., Results: Trial results will be disseminated through peer-reviewed publications and conference presentations., Conclusion: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790)., Competing Interests: Conflict of interest No conflict of interest exists., (Copyright © 2020 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Objective: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population., Design: Post hoc analysis of a multicenter randomized trial., Setting: Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries., Participants: The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate <60 mL/min/1.73 m 2 and perioperative myocardial dysfunction., Interventions: Patients were assigned randomly to receive levosimendan (0.025-0.2 μg/kg/min) or placebo in addition to standard inotropic treatment., Measurements and Main Results: Forty-six patients were assigned to receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14 (30%) patients in the levosimendan group versus 23 (52%) in the placebo group (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035). The incidence of major complications also was lower (18 [39%]) in the levosimendan group versus that in the placebo group (29 [66%]) (absolute difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum creatinine at intensive care unit discharge was observed in the levosimendan group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76] mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07)., Conclusions: Levosimendan may improve renal outcome in cardiac surgery patients with chronic kidney disease undergoing mitral valve surgery who develop perioperative myocardial dysfunction. Results of this exploratory analysis should be investigated in future properly designed randomized controlled trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality., Design and Setting: A web-based international consensus conference., Participants: The study comprised 500 clinicians from 61 countries., Interventions: A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey., Measurements and Main Results: The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted., Conclusions: The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Importance: No effective pharmaceutical agents have yet been identified to treat acute kidney injury after cardiac surgery., Objective: To determine whether fenoldopam reduces the need for renal replacement therapy in critically ill cardiac surgery patients with acute kidney injury., Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study from March 2008 to April 2013 in 19 cardiovascular intensive care units in Italy. We randomly assigned 667 patients admitted to intensive care units after cardiac surgery with early acute kidney injury (≥50% increase of serum creatinine level from baseline or oliguria for ≥6 hours) to receive fenoldopam (338 patients) or placebo (329 patients). We used a computer-generated permuted block randomization sequence for treatment allocation. All patients completed their follow-up 30 days after surgery, and data were analyzed according to the intention-to-treat principle., Interventions: Continuous infusion of fenoldopam or placebo for up to 4 days with a starting dose of 0.1 μg/kg/min (range, 0.025-0.3 µg/kg/min)., Main Outcomes and Measures: The primary end point was the rate of renal replacement therapy. Secondary end points included mortality (intensive care unit and 30-day mortality) and the rate of hypotension during study drug infusion., Results: The study was stopped for futility as recommended by the safety committee after a planned interim analysis. Sixty-nine of 338 patients (20%) allocated to the fenoldopam group and 60 of 329 patients (18%) allocated to the placebo group received renal replacement therapy (P = .47). Mortality at 30 days was 78 of 338 (23%) in the fenoldopam group and 74 of 329 (22%) in the placebo group (P = .86). Hypotension occurred in 85 (26%) patients in the fenoldopam group and in 49 (15%) patients in the placebo group (P = .001)., Conclusions and Relevance: Among patients with acute kidney injury after cardiac surgery, fenoldopam infusion, compared with placebo, did not reduce the need for renal replacement therapy or risk of 30-day mortality but was associated with an increased rate of hypotension., Trial Registration: clinicaltrials.gov Identifier: NCT00621790.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence., Design and Setting: A web-based international consensus conference., Participants: More than 1,000 physicians from 77 countries participated in this web-based consensus conference., Interventions: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials., Measurements and Main Results: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality., Conclusions: Future research and health care funding should be directed toward studying and evaluating these interventions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first international consensus conference on this topic., Methods: The consensus was a continuous international internet-based process with a final meeting on June 28th 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting and ranking., Results: Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, the use of preoperative intra-aortic balloon counterpulsation and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated., Conclusion: This international consensus conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.