HELLO: a protocol for a cluster randomized controlled trial to enhance interpersonal relationships and team cohesion among ICU healthcare professionals.

BACKGROUND: Mental health symptoms among healthcare professionals (HCP) in intensive care units (ICUs) are a significant concern affecting both HCP well-being and patient care outcomes. Cross-sectional studies among members of the European Society of Intensive Care Medicine (ESICM) report up to 50% burnout rates. Determinants of burnout include communication, team cohesion, psychological support, and well-being promotion. We designed the 'Hello Bundle' intervention to mitigate burnout among ICU-HCPs by fostering positive social interactions and a supportive work environment. This justification synthesizes evidence from social psychology, positive psychology, and healthcare communication research to support the intervention. The 'Hello Bundle' aims to enhance interpersonal relationships, improve team cohesion, and reduce burnout rates. The six components include: Hello campaign posters, email reminders, integrating greetings in morning huddles, hello jars, lead-by-example initiatives, and a daily updated hello board in each ICU. This protocol describes a cluster randomized controlled trial to evaluate the effectiveness of the intervention. METHODS: This protocol describes a cluster randomized controlled trial (RCT) conducted among ESICM-affiliated ICUs, consisting of at least 73 clusters with in average of 50 respondents per cluster, totaling approximately 7300 participants. Intervention clusters will implement the 6-component Hello Bundle between October 14 and November 10, 2024, while control clusters will be wait-listed to receive the intervention in January 2025 after the RCT concludes. Clusters will be matched based on ICU size (fewer or more than 20 beds), region, and average 2023 mortality. The primary outcome is the proportion of HCPs with burnout between intervention and control clusters at the end of the intervention. Secondary outcomes include comparing the following between clusters: (1) number of HCPs with high emotional exhaustion; (2) number with high depersonalization; (3) number with loss of accomplishment; (4) perception of ethical climate (5) satisfaction at work (VAS); (6) professional conflicts; (7) intention to leave the ICU (VAS); (8) patient-centered care rating; (9) family-centered care rating. The last secondary outcome is the comparison of burnout rates before and after the intervention in the intervention cluster. Outcomes will be based on HCP reports collected within four weeks before and after the intervention. DISCUSSION: This is the first large trial of healthcare communication, social, and positive psychology intervention among ICU-HCPs. It holds the potential to provide valuable insights into effective strategies for addressing burnout in ICU settings, ultimately benefiting both HCPs and patients. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.Gov on June 18, 2024. REGISTRATION: NCT06453616.

Environmental sustainability in intensive care: the path forward. An ESICM Green Paper.

PURPOSE: The European Society of Intensive Care Medicine (ESICM) Green Paper aims to address the challenge of environmental sustainability in intensive care and proposes actionable strategies for integrating sustainability into intensive care unit (ICU) stakeholder actions. METHODS: The ESICM Executive Committee appointed a task force of topic experts and ESICM committee representatives to develop the ESICM Green Paper. The task force convened biweekly from January to June 2024, identifying key domains for environmental sustainability and prioritizing actions. Drafts were iteratively refined and approved by the ESICM Executive Committee. RESULTS: Climate change will impact activities in intensive care in many ways, but also the impact of ICU activities on the environment is considerable; drivers for this include extensive resource use and waste generation in ICUs from energy consumption, use of disposable items, and advanced therapies for critically ill patients. The ESICM Green Paper outlines a structured approach for ICUs to reduce their environmental impact, emphasizing energy efficiency, waste reduction, and sustainable procurement. Furthermore, it endorses the need for awareness and education among healthcare professionals, integration of sustainability into research, and sustainable policies within scientific societies. CONCLUSIONS: The ESICM Green Paper reviewed the relevance of climate change to intensive care and provided suggestions for clinical practice, research, education, and ESICM organizational domains. It underscores that reducing intensive care's ecological footprint can coexist with high-quality patient care. Promoting a resilient, responsible healthcare system is a joint responsibility of all ICU stakeholders.

Preferences for albumin use in adult intensive care unit patients with shock: An international survey.

INTRODUCTION: Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians. METHODS: We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the use versus no use of albumin. RESULTS: A total of 1248 respondents participated, with a mean response rate of 37%, ranging from 18% to 75% across 21 countries. Respondents mainly worked in mixed ICUs and 92% were specialists in intensive care medicine. The reported use of albumin in general shock varied as 18% reported 'almost never', 22% 'rarely', 34% 'occasionally', 22% 'frequently' and 4% 'almost always' using albumin. In septic shock, 19% reported 'almost never', 22% 'rarely', 29% 'occasionally', 22% 'frequently' and 7% 'almost always' using albumin. Physicians' preferences were more consistent for haemorrhagic- and cardiogenic shock, with more than 45% reporting 'almost never' using albumin. While the reported use of albumin for other purposes than resuscitation was infrequent (40%-85% reported 'almost never' for five other indications), the most frequent other indications were low serum albumin levels and improvement of the efficacy of diuretics. Most respondents (93%) would randomise adult ICU patients with shock to a trial of albumin versus no albumin. CONCLUSIONS: In this international survey, the reported preferences for the use of albumin in adult ICU patients with shock varied considerably among surveyed ICU physicians. The support for a future randomised trial was high.

The impact of the massive open online course C19_SPACE during the COVID-19 pandemic on clinical knowledge enhancement: a study among medical doctors and nurses.

PURPOSE: During the initial phase of the pandemic, healthcare professionals faced difficulties due to the limited availability of comprehensive learning resources on managing patients affected with coronavirus disease 2019 (COVID-19). The COVID-19 Skills Preparation Course (C19_SPACE) was tailored to meet the overwhelming demand for specialized training. The primary objective of this study was to assess the efficacy and impact of this program on enhancing clinical knowledge and to identify factors affecting this improvement. METHODS: As part of the project, data were collected prospectively to measure the baseline knowledge. After the descriptive statistics, multiple and multivariate logistic regression models were executed to identify the factors associated with knowledge increase. RESULTS: The final sample included 3140 medical doctors (MDs) and 3090 nurses (RNs). For the primary analysis, the mean value of the baseline knowledge test score of MDs was 62.41 (standard deviation, SD = 13.48), and it significantly (p < 0.001) increased to 84.65 (SD = 11.95). Factors influencing overall knowledge scores were female sex (AOR = 1.34 [1.04-1.73]), being a specialist qualified for intensive care medicine (adjusted odds ratio, AOR = 0.56, [0.33-0.96]), and performance on the pre-test (AOR = 0.91, [0.90-0.92]). As for the RNs, the mean value of the total knowledge score was 63.25 (SD = 13.53), which significantly (p < 0.001) increased to 81.51 (SD = 14.21). Factor associated with knowledge was performance on the pre-test (AOR = 0.92 [0.92-0.93]). CONCLUSIONS: C19_SPACE effectively increased the clinical knowledge of doctors and nurses. The effect was more pronounced in the program's target group of healthcare workers with less experience in the intensive care unit (ICU). Other factors associated with knowledge enhancement were sex and being a specialist in intensive care.

A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis.

Variability in forgoing life-sustaining treatment practices in critically Ill patients with hospital-acquired bloodstream infections: a secondary analysis of the EUROBACT-2 international cohort.

BACKGROUND: The decision to forgo life-sustaining treatment in intensive care units (ICUs) is influenced by ethical, cultural, and medical factors. This study focuses on a population of patients with hospital-acquired bloodstream infections (HABSI) to investigate the association between patient, pathogen, center and country-level factors and these decisions. METHODS: We analyzed data from the EUROBACT-2 study (June 2019-January 2021) from 265 centers worldwide, focusing on non-COVID-19 patients who died in the hospital or within 28 days after HABSI. We assessed whether death was preceded by a decision to forgo life-sustaining treatment, examining country, center, patient, and pathogen variables. To assess the association of each potentially important variable with the decision to forgo life-sustaining treatment, univariable mixed logistic regression models with a random center effect were performed. RESULTS: Among 1589 non-COVID-19 patients, 519 (32.7%) died, with 191 (36.8%) following a decision to forgo life-sustaining treatment. Significant geographical differences were observed, with no reported decisions to forgo life-sustaining treatment in African countries and fewer in the Middle East compared to Western Europe, Australia, and Asia. Once a center effect was considered, only health expenditure (Odds ratio 1.79, 95%CI: 1.45-2.21, p < 0.01) and age (Odds ratio 1.02, 95%CI: 1.002-1.05, p = 0.03) were significantly associated with decisions to forgo life-sustaining treatment, while other patient and pathogen factors were not. CONCLUSION: Economic and regional disparities significantly impact end-of-life decision-making in ICUs. Global policies should consider these disparities to ensure equitable end-of-life care practices.

Antibiotic dose optimisation in the critically ill: targets, evidence and future strategies.

PURPOSE OF REVIEW: To highlight the recent evidence for antibiotic pharmacokinetics and pharmacodynamics (PK/PD) in enhancing patient outcomes in sepsis and septic shock. We also summarise the limitations of available data and describe future directions for research to support translation of antibiotic dose optimisation to the clinical setting. RECENT FINDINGS: Sepsis and septic shock are associated with poor outcomes and require antibiotic dose optimisation, mostly due to significantly altered pharmacokinetics. Many studies, including some randomised controlled trials have been conducted to measure the clinical outcome effects of antibiotic dose optimisation interventions including use of therapeutic drug monitoring. Current data support antibiotic dose optimisation for the critically ill. Further investigation is required to evolve more timely and robust precision antibiotic dose optimisation approaches, and to clearly quantify whether any clinical and health-economic benefits support expanded use of this treatment intervention. SUMMARY: Antibiotic dose optimisation appears to improve outcomes in critically ill patients with sepsis and septic shock, however further research is required to quantify the level of benefit and develop a stronger knowledge of the role of new technologies to facilitate optimised dosing.

Importance of timely and adequate source control in sepsis and septic shock.

Source control is defined as the physical measures undertaken to eliminate the source of infection and control ongoing contamination, as well as restore anatomy and function at the site of infection. It is a key component of the management of patients with sepsis and septic shock and one of the main determinants of the outcome of infections that require source control. While not all infections may require source control, it should be considered in every patient presenting with sepsis; it is applicable and necessary in numerous infections, not only those occurring in the abdominal cavity. Although the biological rationale is clear, several aspects of source control remain under debate. The timing of source control may impact outcome; early source control is particularly relevant for patients with abdominal infections or necrotizing skin and soft tissue infections, as well as for those with more severe disease. Percutaneous procedures are increasingly used for source control; nevertheless, surgery-tailored to the patient and infection-remains a valid option for source control. For outcome optimization, adequate source control is more important than the strategy used. It should be acknowledged that source control interventions may often fail, posing a challenge in this setting. Thus, an individualized, multidisciplinary approach tailored to the infection and patient is preferable.

Prolonged vs Intermittent Infusions of ß-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis.

Importance: There is uncertainty about whether prolonged infusions of ß-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged ß-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of ß-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of ß-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of ß-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged ß-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.

Continuous vs Intermittent ß-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial.

Importance: Whether ß-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a ß-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a ß-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of ß-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990.

No improvement in mortality among critically ill patients with carbapenems as initial empirical therapy and more detection of multi-drug resistant pathogens associated with longer use: a post hoc analysis of a prospective cohort study.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

Family centeredness of care: a cross-sectional study in intensive care units part of the European society of intensive care medicine.

PURPOSE: To identify key components and variations in family-centered care practices. METHODS: A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated family-centeredness, was assessed using a visual analog scale. Additionally, respondents completed the Maslach Burnout Inventory and the Ethical Decision Making Climate Questionnaire to capture burnout dimensions and assess the ethical decision-making climate. RESULTS: The response rate was 53% (respondents from 359/683 invited ICUs who actually open the email); participating healthcare professionals (HCPs) were from Europe (62%), Asia (9%), South America (6%), North America (5%), Middle East (4%), and Australia/New Zealand (4%). The importance of family-centeredness was ranked high, median 7 (IQR 6-8) of 10 on VAS. Significant differences were observed across quartiles of family centeredness, including in visitation policies availability of a waiting rooms, family rooms, family information leaflet, visiting hours, night visits, sleep in the ICU, and in team-family interactions, including daily information, routine day-3 conference, and willingness to empower nurses and relatives. Higher family centeredness correlated with family involvement in rounds, participation in patient care and end-of-life practices. Burnout symptoms (41% of respondents) were negatively associated with family-centeredness. Ethical climate and willingness to empower nurses were independent predictors of family centeredness. CONCLUSIONS: This study emphasizes the need to prioritize healthcare providers' mental health for enhanced family-centered care. Further research is warranted to assess the impact of improving the ethical climate on family-centeredness.

Antimicrobial stewardship and molecular diagnostics: a symbiotic approach to combating resistance in the ED and ICU.

PURPOSE OF REVIEW: This review aims to evaluate the incorporation of rapid molecular diagnostics (RMD) in antimicrobial stewardship programs (ASPs) in the management of patients in the emergency department (ED) and intensive care unit (ICU), highlighting a shift from conventional microbiological diagnostic tests to RMD strategies to optimize antimicrobial use and improve patient outcomes. RECENT FINDINGS: Recent advances in RMD have demonstrated the superior accuracy of RMD in identifying pathogens, combined with shorter turnaround times. RMD allows speeding up of antimicrobial decision making in the ED and facilitates faster escalation when empirical therapy was inappropriate, as well as more efficient de-escalation of empirical therapy later in the course of the treatment. Implementation of RMD however may be challenging. SUMMARY: RMD hold great value in simplifying patient management and mitigating antimicrobial exposure, particularly in settings with high levels of antimicrobial resistance where the use of broad-spectrum antimicrobials is high. While the impact on the use of antimicrobials is significant, the impact on patient outcomes is not yet clear. Successful integration of RMD in clinical decision making in the ED and ICU requires a team approach and continued education, and its use should be adapted to the local epidemiology and infrastructure.

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.