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Abstract Background Postoperative pain delays ambulation, extends hospital stay, reduces the probability of recovery, and increases risk of long-term functional impairment. Pain management in hip fractured patients poses a challenge to the healthcare teams. Older adults are more vulnerable to opioid-associated side effect and it is primordial to minimize their exposure to opioids. Acetaminophen is associated with reduced opioid use so we need to focus on acetaminophen use in first-line analgesia. Methods We conducted a controlled before/after study to assess the ability of an audit and feedback (A&F) intervention built with nurses to improve the quality of perioperative pain management in older patients hospitalized for hip fracture in an orthogeriatric unit (experimental group) versus a conventional orthopedic unit (no A&F intervention). The primary endpoint was the percentage of patients who received 3 g/day of acetaminophen during the three postoperative days, before and after the A&F intervention. Secondary endpoints included nurses’ adherence to medical prescriptions, clinical data associated with patients and finally factors associated with intervention. The significative level was set at 0.05 for statistical analysis. Results We studied data from 397 patients (mean age 89 years, 75% female). During the postoperative period, 16% of patients from the experimental group received 3 g/day of acetaminophen before the A&F intervention; the percentage reached 60% after the intervention. The likelihood of receiving 3 g/day of acetaminophen during the postoperative period and adhering to the medical prescription of acetaminophen were significantly increased in the experimental group as compared with the control group. The patient’s functional status at discharge (assessed by Activities of Daily Living scores) was significantly better and the length of hospital stay significantly reduced after the A&F intervention. Conclusion Our controlled before/after study showed that an A&F intervention significantly improved perioperative pain management in older adults hospitalized for hip fracture. Involving teams in continuous education programs appears crucial to improve the quality of pain management and ensure nurses’ adherence to medical prescriptions.

Christos Tsamasiotis,1 Gaelle Fiard,2 Pierre Bouzat,3 Patrice François,1 Guillaume Fond,4 Laurent Boyer,4 Bastien Boussat1,5 1Department of Clinical Epidemiology, Grenoble-Alps University Hospital; Laboratory TIMC-IMAG, UMR 5525 Joint Research Unit, National Center for Scientific Research, Faculty of Medicine, Grenoble Alps University, Grenoble, France; 2Department of Urology, Grenoble Alpes University Hospital, CNRS, Grenoble INP, TIMC, Université Grenoble Alpes, Grenoble, France; 3Department of Anaesthesia and Intensive Care, Centre Hospitalier Universitaire Grenoble, University Grenoble Alpes; INSERM U1216, Grenoble Institut Neurosciences, Grenoble, France; 4AP-HM, Aix-Marseille University, School of Medicine - La Timone Medical Campus, UR3279: Health Service Research and Quality of Life Center (CEReSS), Marseille, France; 5O’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, CanadaCorrespondence: Bastien Boussat, Service d’épidémiologie et évaluation médicale, CHU Grenoble-Alpes, Boulevard de la Chantourne, La Tronche, 38700, France, Tel +33 4 76 76 69 96, Email bboussat@chu-grenoble.frBackground: Given the increasing focus on patient safety in healthcare systems worldwide, understanding the impact of Continuous Quality Improvement Programs (QIPs) is crucial. QIPs, including Morbidity and Mortality Conferences (MMCs) and Experience Feedback Committees (EFCs), have been identified as effective strategies for enhancing patient safety culture. These programs engage healthcare professionals in the identification and analysis of adverse events to foster a culture of safety (ie the product of individual and group value, attitudes, and perceptions about quality and safety). This study aimed to determine whether patient safety culture differed regarding care provider participation in MMCs and EFCs activities.Methods: A cross-sectional web-only survey was conducted in 2022 using the Hospital Survey on Patient Safety Culture (HSOPS) among 4780 employees at an 1836-bed, university-affiliated hospital in France. We quantified the mean differences in the 12 HSOPS dimension scores according to MMCs and EFCs participation, using Cohen d effect size. We performed a multivariate analysis of variance to examine differences in dimension scores after adjusting for background characteristics.Results: Of 4780 eligible employees, 1457 (30.5%) participated in the study. Among the respondents, 571 (39.2%) participated in MMCs or EFCs activities. Participants engaged in MMCs or EFCs reported significantly higher scores in six out of twelve HSOPS dimensions, particularly in “Nonpunitive response to error”, “Feedback and communication about error”, and “Organizational learning” (Overall effect size = 0.14, 95% confidence interval = 0.11 to 0.17, P< 0.001). Notably, involvement in both MMCs and EFCs was associated with higher improvements in patient safety culture compared to non-participation or singular involvement in either program. However, certain dimensions such as “Staffing”, “Hospital management support”, and “Hospital handoffs and transition” showed no significant association with MMCs or EFCs participation, highlighting broader systemic challenges.Conclusion: The study confirms the positive association between participation in MMCs or EFCs and an enhanced culture of patient safety, emphasizing the importance of such programs in fostering an environment conducive to learning, communication, and nonpunitive responses to errors. While MMCs or EFCs are effective in promoting certain aspects of patient safety culture, addressing broader systemic challenges remains crucial for comprehensive improvements in patient safety.Keywords: patient safety culture, quality improvement programs, morbidity and mortality conferences, experience feedback committees

Abstract Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE−). Blood samples were collected from 30 EE+ and 15 EE− in La Rinconada (Peru, 5100–5300 m a.s.l.), with special attention given to the sampling pre‐analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet‐poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE− and LL (all P

Objetivo: Reportar la sensibilidad al cambio e interpretabilidad de la versión argentina de la escala de catastrofización del dolor (PCS-Arg, por sus siglas en inglés) en una muestra de sujetos con dolor lumbar crónico (DLC). Materiales y métodos: Estudio prospectivo, observacional y longitudinal. Se reclutaron sujetos con DLC derivados a la unidad de kinesiología de un hospital público de la Ciudad Autónoma de Buenos Aires. Inicialmente, se registraron los datos demográficos y las puntuaciones de la PCS-Arg, así como la intensidad del dolor, discapacidad, calidad de vida y depresión mediante cuestionarios autoadministrados. En segunda instancia, al mes o alta del tratamiento, se repitieron los cuestionarios junto con una escala global de cambio. La sensibilidad al cambio fue evaluada mediante la validez de constructo longitudinal. La interpretabilidad se calculó mediante el método basado en el ancla, y se reportaron la diferencia mínima clínicamente importante (DMCI) y el beneficio clínico sustancial (BCS). Resultados: Se incluyeron 102 sujetos. La PCS-Arg demostró una sensibilidad al cambio aceptable. La DMCI fue de 10 puntos, con un área bajo la curva (AUC) de 0,65 y un intervalo de confianza del 95 % (IC95% 0,47-0,83). El BCS fue de 17 puntos, con un AUC de 0,66 (IC95% 0,55-0,77). Conclusión: La PCS-Arg es un instrumento sensible al cambio. La capacidad discriminativa de los valores para identificar la DMCI y el BCS fue pobre. Estos resultados permitirán interpretar el impacto de diferentes terapéuticas orientadas a modificar el catastrofismo, así como potenciar futuros ensayos clínicos que incluyan sujetos con DLC.

The Caenorhabditis elegans egg hatching methodology is a valuable tool for assessing the anthelmintic activity of drugs and compounds and evaluating anthelmintic drug efficacy.Isolated eggs from gravid adults are exposed to different concentrations of selected drugs and the percentage of egg hatching is determined with respect to the control condition. The assay allows the construction of concentration-response curves and determination of EC50 or EC90 values for egg hatching inhibition. Also, it allows measurements of inhibition as a function of time of exposure.This approach addresses the urgent need for new anthelmintics, as resistance to current treatments poses a significant challenge in parasitic nematode infection. This resistance not only affects humans but also animals and plants, causing significant economic losses in livestock farming and agriculture.By using the free-living nematode C. elegans as a parasitic model organism, researchers can efficiently screen for potential treatments and assess drug combinations for synergistic effects. Importantly, this assay offers a cost-effective and accessible alternative to traditional methods, eliminating the need for specialized infrastructure, hosts, and trained animal maintenance personnel. Additionally, the methodology closely mimics natural conditions, providing insights into egg development and potential therapeutic targets.This method allows for evaluating the direct negative impact of drugs on egg hatching, which correlates with long-term anthelmintic effects, offering advantages in preventing or reducing the transmission and spread of worm infections by eggs.Overall, this approach represents a significant advancement for anthelmintic discovery, offering both practical applications and avenues for further scientific research. • The C. elegans egg hatching assay is a robust and effective method for assessing the anthelmintic potential of various drugs and compounds, allowing the generation of concentration-response curves. • By leveraging the free-living nematode C. elegans as a parasitic model organism, this method facilitates efficient screening of potential treatments and evaluation of drug combinations. • The method addresses the urgent need for new anthelmintics, offering a cost-effective and accessible alternative to traditional approaches.

Abstract Background The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. Methods A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. Results A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). Conclusions This consensus provides practical recommendations to support a clinician’s decision making in the management of tSCI polytrauma patients.

BackgroundThe COVID-19 pandemic had a global impact on people life, notably because of lockdown periods. This could particularly affected patients suffering from hip fracture, who could have been more isolated during these periods. We aim at evaluating the impact of the COVID-19 period (including lockdown periods) on quality of life (QOL) in older adult patients 90 days after a surgery for a hip fracture.Subject and methodsAncillary study of the prospective randomized controlled HiFIT study. We compared the QOL measured at 90 days after a hip fracture surgery using the EuroQOL-5 dimensions 3 levels (EQ-5D), the Perceived Quality of life (PQOL) and the Instrumental Activities of Daily Living (IADL) in patients included in the Hifit study before and during the COVID-19 pandemic.ResultsThe characteristics of the 161 patients included before and of the 213 included during the COVID period (including 122 (57%) during COVID with containment periods and 91 (43%) during COVID without containment periods) were similar (mean age 84 ± 10 years; 282 (75%) women). The majority (81%) of the patients alive at 90 days had returned to their previous place of residence in both periods. During the COVID period, EQ-5D showed better patient pain/discomfort and anxiety/depression levels. The PQOL happiness was not different, with around 81% of the patient being “happy” or “very happy” during the two periods and the IADL was also similar during the two periods. In the multivariate analysis odd ratios of having poorer outcomes were increased before COVID for pain/discomfort (OR 2.38, 95%CI [1.41–4.15], p = 0.001), anxiety (OR 1.89 [1.12–3.21], p = 0.017) and mobility (1.69 [1.02–2.86], p = 0.044).ConclusionPatient’s quality of life measured using different scales was not altered during the COVID period compared to before COVID, 90 days after a hip fracture. Surprisingly, the Pain/Discomfort and Anxiety dimensions of the EQ-5D questionnaires were even better during the COVID period.Clinical trial registration:https://clinicaltrials.gov/ (NCT02972294).

Abstract The prediction of the therapeutic intensity level (TIL) for severe traumatic brain injury (TBI) patients at the early phase of intensive care unit (ICU) remains challenging. Computed tomography images are still manually quantified and then underexploited. In this study, we develop an artificial intelligence-based tool to segment brain lesions on admission CT-scan and predict TIL within the first week in the ICU. A cohort of 29 head injured patients (87 CT-scans; Dataset1) was used to localize (using a structural atlas), segment (manually or automatically with or without transfer learning) 4 or 7 types of lesions and use these metrics to train classifiers, evaluated with AUC on a nested cross-validation, to predict requirements for TIL sum of 11 points or more during the 8 first days in ICU. The validation of the performances of both segmentation and classification tasks was done with Dice and accuracy scores on a sub-dataset of Dataset1 (internal validation) and an external dataset of 12 TBI patients (12 CT-scans; Dataset2). Automatic 4-class segmentation (without transfer learning) was not able to correctly predict the apparition of a day of extreme TIL (AUC = 60 ± 23%). In contrast, manual quantification of volumes of 7 lesions and their spatial location provided a significantly better prediction power (AUC = 89 ± 17%). Transfer learning significantly improved the automatic 4-class segmentation (DICE scores 0.63 vs 0.34) and trained more efficiently a 7-class convolutional neural network (DICE = 0.64). Both validations showed that segmentations based on transfer learning were able to predict extreme TIL with better or equivalent accuracy (83%) as those made with manual segmentations. Our automatic characterization (volume, type and spatial location) of initial brain lesions observed on CT-scan, publicly available on a dedicated computing platform, could predict requirements for high TIL during the first 8 days after severe TBI. Transfer learning strategies may improve the accuracy of CNN-based segmentation models. Trial registrations Radiomic-TBI cohort; NCT04058379, first posted: 15 august 2019; Radioxy-TC cohort; Health Data Hub index F20220207212747, first posted: 7 February 2022.

Las pruebas de salto (PS) son utilizadas con frecuencia como método de evaluación funcional en deportistas con lesiones de miembros inferiores. Actualmente, además de las PS convencionales, se propone incorporar PS verticales. Las mismas, pueden evaluarse mediante pruebas de laboratorio (plataforma de salto) o pruebas de campo (aplicación en smartphone o evaluación clínica). El objetivo de este paso a paso es describir dos pruebas de campo sencillas, confiables, de bajo costo, que se pueden utilizar en la práctica clínica en conjunto con otras pruebas para ayudar a los kinesiólogos a diseñar un programa de rehabilitación o progresión del tratamiento.

Abstract Background Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care. Methods A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted. Results A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided. Conclusions This consensus provides practical recommendations to support clinician’s decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.

Abstract Background Although blood transfusions can be lifesaving in severe hemorrhage, they can also have potential complications. As anemia has also been associated with poor outcomes in critically ill patients, determining an optimal transfusion trigger is a real challenge for clinicians. This is even more important in patients with acute brain injury who were not specifically evaluated in previous large randomized clinical trials. Neurological patients may be particularly sensitive to anemic brain hypoxia because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue oxygen demand. Methods We described herein the methodology of a prospective, multicenter, randomized, pragmatic trial comparing two different strategies for red blood cell transfusion in patients with acute brain injury: a “liberal” strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL and a “restrictive” approach in which the aim is to maintain Hb concentrations greater than 7 g/dL. The target population is patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH). The primary outcome is the unfavorable neurological outcome, evaluated using the extended Glasgow Outcome Scale (eGOS) of 1–5 at 180 days after the initial injury. Secondary outcomes include, among others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the occurrence of extra-cerebral organ dysfunction/failure, and the development of any infection or thromboembolic events. The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome from 50 to 39% between groups (397 patients in each arm). The study was initiated in 2016 in several ICUs and will be completed in December 2022. Discussion This trial will assess the impact of a liberal versus conservative strategy of blood transfusion in a large cohort of critically ill patients with a primary acute brain injury. The results of this trial will help to improve blood product and transfusion use in this specific patient population and will provide additional data in some subgroups of patients at high risk of brain ischemia, such as those with intracranial hypertension or cerebral vasospasm. Trial registration ClinicalTrials.gov NCT02968654.

This study examines the tempo and drivers of penguin diversification by combining genomes from all extant and recently extinct penguin lineages, stratigraphic data from fossil penguins and morphological and biogeographic data from all extant and extinct species. Together, these datasets provide new insights into the genetic basis and evolution of adaptations in penguins.

Nicotinic acetylcholine receptors (nAChRs) comprise a family of pentameric ligand-gated ion channels widely distributed in the central and peripheric nervous system and in non-neuronal cells. nAChRs are involved in chemical synapses and are key actors in vital physiological processes throughout the animal kingdom. They mediate skeletal muscle contraction, autonomic responses, contribute to cognitive processes, and regulate behaviors. Dysregulation of nAChRs is associated with neurological, neurodegenerative, inflammatory and motor disorders. In spite of the great advances in the elucidation of nAChR structure and function, our knowledge about the impact of post-translational modifications (PTMs) on nAChR functional activity and cholinergic signaling has lagged behind. PTMs occur at different steps of protein life cycle, modulating in time and space protein folding, localization, function, and protein-protein interactions, and allow fine-tuned responses to changes in the environment. A large body of evidence demonstrates that PTMs regulate all levels of nAChR life cycle, with key roles in receptor expression, membrane stability and function. However, our knowledge is still limited, restricted to a few PTMs, and many important aspects remain largely unknown. There is thus a long way to go to decipher the association of aberrant PTMs with disorders of cholinergic signaling and to target PTM regulation for novel therapeutic interventions. In this review we provide a comprehensive overview of what is known about how different PTMs regulate nAChR.

Abstract Background Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. Methods This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. Results Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6–40.5%), and Bland–Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7–92.6%) and a specificity of 72% (95% CI 51.9–94.0%) with an AUC of 76% (95% CI 65.6–85.5%). Conclusions and relevance ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration: NCT02322970 .