Search

Lombardy represents the largest region of Italy by population, with almost 10 million residents, a dimension similar to a medium size country like Sweden or Belgium. The CML subcommittee of the Lombardy Hematology Network (REL‐CML) conducted a study at the beginning of 2023. Prevalence was calculated by direct input from the 21 centers participating in REL‐CML. Tyrosine Kinase Inhibitors (TKI) prescription records collected from the ARIA regional registry were used to estimate the number of CML patients followed in smaller centers not participating in REL‐CML. A total of 2285 patients were registered, representing a prevalence of 0.23 ‰. These data were compared to a similar census conducted in 2005, at the beginning of the TKI era, where a prevalence of 0.029‰ was calculated. This indicates that an almost 10 times increase took place during this period of time. Imatinib represents the most frequently prescribed first‐line TKI; its use in 2022 still represented 75% of total first line prescriptions. An increased concentration of the care of CML patients in specialized REL centers with a decreased dispersion of patients in small centers was also evident over this 18 year period of time. Nineteen % of patients discontinued treatment, highlighting persisting logistical and biological challenges; one some recommendations on CML management are included to this aim. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic has been associated with significant variability in acute kidney injury (AKI) incidence, leading to concerns regarding patient heterogeneity. The study's primary objective was a cluster analysis, to identify homogeneous subgroups of patients (clusters) using baseline characteristics, including inflammatory biomarkers. The secondary objectives were the comparisons of MAKE-90 and mortality between the different clusters at three months., Methods: This retrospective single-center study was conducted in the Medical Intensive Care Unit of the University Hospital of Clermont-Ferrand, France. Baseline data, clinical and biological characteristics on ICU admission, and outcomes at day 90 were recorded. The primary outcome was the risk of major adverse kidney events at 90 days (MAKE-90). Clusters were determined using hierarchical clustering on principal components approach based on admission characteristics, biomarkers and serum values of immune dysfunction and kidney function., Results: It included consecutive adult patients admitted between March 20, 2020 and February 28, 2021 for severe COVID-19. A total of 149 patients were included in the study. Three clusters were identified of which two were fully described (cluster 3 comprising 2 patients). Cluster 1 comprised 122 patients with fewer organ dysfunctions, moderate immune dysfunction, and was associated with reduced mortality and a lower incidence of MAKE-90. Cluster 2 comprised 25 patients with greater disease severity, immune dysfunction, higher levels of suPAR and L-FABP/U Creat, and greater organ support requirement, incidence of AKI, day-90 mortality and MAKE-90., Conclusions: This study identified two clusters of severe COVID-19 patients with distinct biological characteristics and renal event risks. Such clusters may help facilitate the identification of targeted populations for future clinical trials. Also, it may help to understand the significant variability in AKI incidence observed in COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mascle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clinical research is essential for the development and progress of therapies and procedures. Intensive care units (ICUs) manage the sickest patients. Numerous clinical trials are organised in ICUs to evaluate new treatments or support techniques. Concomitantly, new professions involved in clinical research set-ups are emerging., Aim: The aim of this scoping review was to identify the nature and extent of research evidence on the organisation of clinical research in ICUs., Methods: This review focusses on observational and qualitative narrative studies dealing with clinical research organisation in ICUs, with a special interest in structures coordinating research, the roles of clinical research professionals, and the training required. Medline and Embase were analysed between January 2000 and June 2024. Assessment of the study quality was based on the Let Evidence Guide Every New Decision evaluation system and the Newcastle-Ottawa quality assessment scale., Results: Of the 14 studies reviewed, four were narrative and 10 observational descriptive. All were based on cross-sectional surveys. Most studies were carried out in North America, the United Kingdom, and Australia/New Zealand. ICU clinical research professionals were mostly female nurses aged between 31 and 50 years who had a wide diversity of training profiles and performed greatly varied tasks from data collection to publication of the article. Reported job satisfaction depended on the degree of autonomy, the workload, the extent of professional recognition, and opportunities for professional promotion., Conclusions: The organisation of ICU clinical research reflects considerable diversity in training, tasks, job organisation, and responsibilities., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: CT-scan and inflammatory and coagulation biomarkers could help in prognostication of COVID-19 in patients on ICU admission., Objective: The objectives of this study were to measure the prognostic value of the extent of lung parenchymal lesions on computed tomography (CT) and of several coagulation and inflammatory biomarkers, and to explore the characteristics of the patients depending on the extent of lung parenchymal lesions., Design: Retrospective monocentric observational study achieved on a dataset collected prospectively., Setting: Medical ICU of the university hospital of Clermont-Ferrand, France., Patients: All consecutive adult patients aged ≥18 years admitted between 20 March, 2020 and 31 August, 2021 for COVID-19 pneumonia., Interventions: Characteristics at baseline and during ICU stay, and outcomes at day 60 were recorded. The extent of lung parenchyma lesions observed on the chest CT performed on admission was established by artificial intelligence software., Measurements: Several clinical characteristics and laboratory features were collected on admission including plasma interleukin-6, HLA-DR monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day-60 mortality were investigated by uni- and multivariate survival analyses., Results: 270 patients were included. Inflammation biomarkers including the levels of neutrophils, CRP, ferritin and Il10 were the indices the most associated with the severity of the extent of the lung lesions. Patients with more extensive lung parenchymal lesions (≥ 75%) on admission had higher CRP serum levels. The extent of lung parenchymal lesions was associated with a decrease in the PaO2/FiO2 ratio(p<0.01), fewer ventilatory-free days (p = 0.03), and a higher death rate at day 60(p = 0.01). Extent of the lesion of more than 75% was independently associated with day-60 mortality (aHR = 1.72[1.06; 2.78], p = 0.03). The prediction of death at day 60 was improved when considering simultaneously biological and radiological markers obtained on ICU admission (AUC = 0.78)., Conclusions: The extent of lung parenchyma lesions on CT was associated with inflammation, and the combination of coagulation and inflammatory biomarkers and the extent of the lesions predicted the poorest outcomes., Competing Interests: no competing of interest, (Copyright: © 2024 Krisht et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture., Methods: We performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality., Results: We included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73)., Conclusions: Antimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures., (© 2024. The Author(s).)

Background: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment., Materials and Methods: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR) 3.0 and to improve Health-Related Quality of Life (HRQoL) in CML elderly patients., Results: A total of 215 patients in stable MR 3.0 /MR 4.0 were randomized to receive an intermittent TKI schedule 1 month ON-1 month OFF for 3 years (FIXED arm; n = 111) vs. a progressive de-escalation TKI dose up to one-third of the starting dose at the 3rd year (PROGRESSIVE arm; n = 104). Two hundred three patients completed the 3rd year of OPTkIMA study. At the last follow-up, MR 3.0 loss was 27% vs. 46% (P = .005) in the FIXED vs PROGRESSIVE arm, respectively. None of these patients experienced disease progression. The 3-year probability of maintaining the MR 3.0 was 59% vs. 53%, respectively (P = .13). HRQoL globally improved from the baseline to the 3rd year, without any significant difference between the 2 arms. After the 3rd year, the proportion of patients who was address to TKI discontinuation in the 2 arms was 36% (FIXED) vs. 58% (PROGRESSIVE) (P = .03)., Conclusions: The intensification of intermittent TKI therapy is associated with a higher incidence of MR 3.0 loss, but those patients who maintain the MR 3.0 molecular response at the end of the study have been frequently considered eligible for TFR. The HRQoL generally improved during the de-escalation therapy in both randomization arms., Competing Interests: Disclosures AI: Speaker honoraria – AOP, BMS, GSK, Incyte, Novartis and Pfizer. CB: Speaker's Bureau – Novartis, Incyte and Pfizer AB: Advisory Board and Consultancy - Novartis, Incyte, BMS, Pfizer. GR: Speaker's Bureau and Advisory Boards - Incyte, Novartis and Pfizer. MT: Speaker's Bureau – Novartis, Incyte and BMS. AMR: research funding - AstraZeneca, European Hematology Association, Transcan2-ERANET and Italian Association for Cancer Research (Fondazione AIRC); honoraria - Amgen, Celgene, Janssen and Takeda. All the other Authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of information about the organisation and management of clinical research personnel in Europe and of their professional activity in intensive care. We therefore conducted a cross-sectional survey among personnel currently working in a French intensive care research network that involves 41 centres nationwide. The aim of the survey was to describe the personnel's personal and institutional organisation and management, their job perception in terms of satisfaction and stress, and suggestions for improvement., Methods: Over 3 months in 2023, the research personnel received an electronic questionnaire on their personal and professional profile, past and present training, workplace and functions currently performed, personal knowledge about job skills required, job satisfaction and stress by as measured on a rating scale, and suggested ways of improvement., Results: Ninety seven people replied to the questionnaire (a response rate of 71.3%), of whom 78 (57.3%) were sufficiently involved in intensive care to provide complete answers. This core sample had profiles in line with French recruitment policies and comprised mainly Bachelor/Master graduates, with nurses accounting for only 21.8%. The female to male ratio was 77:23%. Many responders declared to have a shared activity of technician (for investigation) and assistant (for quality control). More than 70% of the responders considered that most of the tasks required of each worker were major. Figures were much lower for project managers, who were few to take part in the survey. On a scale of 10, the median of job satisfaction was 7 for personal work organisation, 6 for training and for institutional organisation, and only 5 for personal career management. The median of job stress was 5 and was inversely correlated with satisfaction with career management. Respect of autonomy, work-sharing activity between investigation and quality control, a better career progression, financial reward for demanding tasks, and participation in unit staff meetings were the main suggestions to improve employee satisfaction., Conclusion: This nationwide survey provides a new insight into the activity of French clinical research personnel and points to ways to improve the quality and efficiency of this workforce., (© 2024. The Author(s).)

Abstract: A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background : Few data are available concerning the outcome of patients denied venovenous extracorporeal membrane oxygenation (VV-ECMO) relative to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Methods : We compared the 90-day survival rate of consecutive adult patients for whom our center was contacted to discuss VV-ECMO indication. Three groups of patients were created: patients for whom VV-ECMO was immediately indicated (ECMO-indicated group), patients for whom VV-ECMO was not indicated at the time of the call (ECMO-not-indicated group), and patients for whom ECMO was definitely contraindicated (ECMO-contraindicated group). Results : In total, 104 patients were referred for VV-ECMO support due to severe COVID-19 ARDS. Among them, 32 patients had immediate VV-ECMO implantation, 28 patients had no VV-ECMO indication, but 1 was assisted thereafter, and 44 patients were denied VV-ECMO for contraindication. Among the 44 patients denied, 30 were denied for advanced age, 24 for excessive prior duration of mechanical ventilation, and 16 for SOFA score >8. The 90-day survival rate was similar for the ECMO-indicated group and the ECMO-not-indicated group at 62.1 and 61.9%, respectively, whereas it was significantly lower (20.5%) for the ECMO-contraindicated group. Conclusions : Despite a low survival rate, 50% of patients were at home 3 months after being denied for VV-ECMO for severe ARDS due to COVID-19.

Objectives: This study sought to determine the economic cost of the management of glaucoma among patients seeking care in health facilities in Ghana., Design: A cross-sectional cost-of-illness (COI) study from the perspective of the patients was employed., Setting: The study was conducted in public and private eye care facilities in the Tema Metropolis of Ghana., Participants: About 180 randomly selected glaucoma patients seeking healthcare at two facilities participated in the study., Main Outcome Measure: Direct cost, including medical and non-medical costs, indirect cost, and intangible burden of management of glaucoma., Results: the cost per patient treated for glaucoma in both facilities was US$60.78 (95% CI: 18.66-107.80), with the cost in the public facilities being slightly higher (US$62.50) than the private facility (US$ 59.3). The largest cost burden in both facilities was from direct cost, which constituted about 94% of the overall cost. Medicines (42%) and laboratory and diagnostics (26%) were the major drivers of the direct cost. The overall cost within the study population was US$10,252.06. Patients paid out of pocket for the frequently used drug- Timolol, although expected to be covered under the National Health Insurance Scheme (NHIS). Patients, however, expressed moderate intangible burdens due to glaucoma., Conclusion: The cost of the management of glaucoma is high from the perspective of patients. The direct costs were high, with the main cost drivers being medicines, laboratory and diagnostics. It is recommended that the National Health Insurance Authority (NHIA) should consider payment for commonly used medications to minimize the burden on patients., Funding: None declared., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Background: Inconsistent results from COVID-19 studies raise the issue of patient heterogeneity., Objective: The objective of this study was to identify homogeneous subgroups of patients (clusters) using baseline characteristics including inflammatory biomarkers and the extent of lung parenchymal lesions on CT, and to compare their outcomes., Design: Retrospective single-center study., Setting: Medical ICU of the University Hospital of Clermont-Ferrand, France., Patients: All consecutive adult patients aged greater than or equal to 18 years, admitted between March 20, 2020, and August 31, 2021, for COVID-19 pneumonia., Interventions: Characteristics at baseline, during ICU stay, and outcomes at day 60 were recorded. On the chest CT performed at admission the extent of lung parenchyma lesions was established by artificial intelligence software., Measurements and Main Results: Clusters were determined by hierarchical clustering on principal components using principal component analysis of admission characteristics including plasma interleukin-6, human histocompatibility leukocyte antigen-DR expression rate on blood monocytes (HLA-DR) monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day 60 mortality were investigated by univariate survival analysis. Two hundred seventy patients were included. Four clusters were identified and three were fully described. Cluster 1 (obese patients, with moderate hypoxemia, moderate extent of lung parenchymal lesions, no inflammation, and no down-regulation of mHLA-DR) had a better prognosis at day 60 (hazard ratio [HR] = 0.27 [0.15-0.46], p < 0.01), whereas cluster 2 (older patients with comorbidities, moderate extent of lung parenchyma lesions but significant hypoxemia, inflammation, and down-regulation of mHLA-DR) and cluster 3 (patients with severe parenchymal disease, hypoxemia, inflammatory reaction, and down-regulation of mHLA-DR) had an increased risk of mortality (HR = 2.07 [1.37-3.13], p < 0.01 and HR = 1.52 [1-2.32], p = 0.05, respectively). In multivariate analysis, only clusters 1 and 2 were independently associated with day 60 death., Conclusions: Three clusters with distinct characteristics and outcomes were identified. Such clusters could facilitate the identification of targeted populations for the next trials., Competing Interests: This study was supported by a grant from Michelin Corporate Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Evrard received funding from Thermo Fisher Diagnostics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Smart Grid (SG) technology utilizes advanced network communication and monitoring technologies to manage and regulate electricity generation and transport. However, this increased reliance on technology and connectivity also introduces new vulnerabilities, making SG communication networks susceptible to large-scale attacks. While previous surveys have mainly provided high-level overviews of SG architecture, our analysis goes further by presenting a comprehensive architectural diagram encompassing key SG components and communication links. This holistic view enhances understanding of potential cyber threats and enables systematic cyber risk assessment for SGs. Additionally, we propose a taxonomy of various cyberattack types based on their targets and methods, offering detailed insights into vulnerabilities. Unlike other reviews focused narrowly on protection and detection, our proposed categorization covers all five functions of the National Institute of Standards and Technology cybersecurity framework. This delivers a broad perspective to help organizations implement balanced and robust security. Consequently, we have identified critical research gaps, especially regarding response and recovery mechanisms. This underscores the need for further investigation to bolster SG cybersecurity. These research needs, among others, are highlighted as open issues in our concluding section., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)