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Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model’s original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell’s adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model’s original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p

Introduction: We established a patient centric navigation model embedded in primary care (PC) to support access to the broad range of health and social resources; the Access to Resources in the Community (ARC) model. Methods: We evaluated the feasibility of ARC using the rapid cycle evaluations of the intervention processes, patient and PC provider surveys, and navigator log data. PC providers enrolled were asked to refer patients in whom they identified a health and/or social need to the ARC navigator. Results: Participants: 26 family physicians in four practices, and 82 of the 131 patients they referred. ARC was easily integrated in PC practices and was especially valued in the non-interprofessional practices. Patient overall satisfaction was very high (89%). Sixty patients completed the post-intervention surveys, and 33 reported accessing one or more service(s). Conclusion: The ARC Model is an innovative approach to reach and support a broad range of patients access needed resources. The Model is feasible and acceptable to PC providers and patients, and has demonstrated potential for improving patients’ access to health and social resources. This study has informed a pragmatic randomized controlled trial to evaluate the ARC navigation to an existing web and telephone navigation service (Ontario 211).

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.

Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p

The term autopoiesis was coined to describe the regenerating and self-maintaining chemical systems of cells. The term has subsequently been applied to many different fields, including sociology, systems theory and information systems. This theory postulates that an autopoietic unity (cell, machine) is an organised network of processes that exists in a delimited space, which produces components which in turn continuously regenerate and create the network of processes that produced them. The Santiago Theory of Cognition grew from the Theory of Allopoiesis stating that all living systems are cognitive systems, and the process of living is a process of cognition. Cognition is the ability to adapt to a certain environment and cognition emerges because of a continuous bilateral interaction between the system and its environment. The resultant complexity seen in living systems is caused by this interaction between the system and its environment. Autopoiesis and cognition are however opposing concepts because cognition can only exist when the system is open and not closed as autopoiesis suggests. It is also difficult to see how autopoietic systems could originate if they are closed and how the continuous change which we see in evolution can be explained if life consists of autopoietic systems. It is postulated that cells and organisms are in fact open systems relating genetically to ancestors before them and their ever-changing descendants after them and the flow of molecules and energy through an ever-changing ecology.

A new fossil site was discovered in the Rising Star Cave in 2013 in the Cradle of Humankind in South Africa. This site which has yielded 1550 hominin bones so far is considered to be one of the richest palaeoanthropological sites in the world. The deposition of the fossils in a remote part of the cave system, approximately 100 m from the entrance, has resulted in a great deal of speculation. The relative inaccessibility of the site and the number of fossil bones it contained and the fact that virtually all these bones were those of a single species of hominid led to the conclusion that the bones were not deposited because of natural sedimentary processes, but that these phenomena were evidence of purposeful disposal or even burial of the dead by hominins. If this assumption is true, it would be the earliest evidence of a metaphysical awareness in humankind. The tenuous evidence on which this hypothesis rests will be discussed and a more plausible alternative explanation where water and gravity were responsible for the deposition of the remains is forwarded.

Nature is paramount to our existence. Humankind clearly realised the importance of nature since the beginning of our sapient abilities. Archaeological evidence shows how humans revered nature and how natural phenomena were mystified. This mystification of nature inspired animism and many associated religious rites, some of which are still part of our cultural existence. Some of the important results that stemmed from the mystification of nature is that it was seen as either good, being the handiwork of God or Gods, or that it started out as perfect but then became bad after the fall. Scientific research however show that there is no morality or hidden codes in nature, but that nature consists of random events, some which benefit humans, while others do not. Parasitology serves as a good example to show how extremely non-humane nature can be and how naïve and idealised our view of nature is. Not only did parasites exist on the planet since the beginning of life on earth and long before the existence of hominins, but the majority of all known animals are parasites. The latest research shows that parasites have a very important role in the ecology and that life as it exists would not have been possible without them. This implies that our romanticised ideas of ecology, biodiversity, the morality of nature and the purpose of life should be reviewed.

Mining and, especially, gold and uranium mining have played a major role in the economy, history, and demography of South Africa. The contribution of the mines to the economy of South Africa over the past century has been overvalued, while the social injustices and negative environmental impacts that accompanied mining have been underplayed or ignored by the mining houses and government. The environmental situation has worsened significantly over the past few years due to the abandonment and pending closure of most of these mines. A reluctance is perceived on the part of the mining companies, and even government, to take responsibility for the damage caused by pollution, ecological degradation, and impact on human health by mining. Instead, the current informal policy appears to take smaller companies to court on minor environmental injustices to, perhaps, impress the broader public, while one of the biggest environmental concerns is stylishly treated. The inability of government to address the damage by mines effectively is in conflict with the National Water Act, the National Environmental Management Act, the Mineral and Petroleum Resources Act, the National Nuclear Regulator Act, and the Constitution of South Africa. The authors propose a multidisciplinary approach to address water-related environmental injustices on the West Rand and Far West Rand. We also describe the application of the National Environmental Management Act of South Africa (Act No. 107 of 1998) in the Wonderfonteinspruit and Tweelopiespruit Catchments and the current water quality situation.

Background & Aims: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis. Methods: We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event. Results: The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG

BackgroundThe Human Immunodeficiency Virus (HIV) epidemic remains active among women in Europe, with significant missed opportunities for HIV testing. Although HIV testing falls within the scope of Family Planning Centers (FPCs), it is often not offered. This pilot study assessed the feasibility and acceptability of systematically offering HIV rapid testing by non-physician professionals, independent of medical appointments, to visitors and accompanying persons in FCPs.MethodsIn September 2020, three FPCs in the Paris region were selected for a 6-month pilot based on high local HIV diagnosis rates among women and the absence of an existing HIV rapid testing offer. A dedicated midwife coordinated a certified training course for non-physician professionals, including group discussions on obstacles and facilitators for offering HIV rapid testing, education on HIV and the use of HIV rapid tests, and the development of procedures, including a standardized HIV questionnaire, to systematically offer HIV rapid testing. We measured participation rates in the study and acceptability of the HIV rapid testing offer. We analyzed visitor characteristics, HIV risk factors and knowledge about HIV.ResultsAll non-physician professionals across the three FPCs were trained. HIV rapid testing was systematically offered to 261 incoming visitors and accompanying persons from September 2020 to March 2021: 93% completed the questionnaire, and 91% accepted the HIV rapid testing offer; 63% reported prior HIV risk behaviors. Visitors born in North Africa had the least knowledge about HIV. Twenty-two visitors declined the testing offer, citing recent HIV testing, no perceived lack of risk, feeling unprepared, or fear of the outcome.ConclusionThe results demonstrate the feasibility and strong acceptability of systematically offering HIV rapid testing by non-physician professionals in large urban FPCs. Extending this approach to include sexually transmitted infections (STIs) screening could be beneficial.

Background & Aims: The fragility index (FI), i.e., theminimum number of best survivors reassigned to the control group required to revert the statistically significant result of a clinical trial to non-significant, is a metric to evaluate the robustness of randomized controlled trials (RCTs). We aimed to assess the FI in the field of HCC. Methods: This is a retrospective analysis of phase 2 and 3 RCTs for the treatment of HCC published between 2002 and 2022. We included two-arm studies with 1:1 randomization and significant positive results for a primary time-to-event endpoint for the FI calculation, which involves the iterative addition of a best survivor from the experimental group to the control group, until positive significance (p

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Abstract Background Given the importance of continuous learning as a response to the increasing complexity of health care practice, there is a need to better understand what makes communities of practice in health effective at fostering learning. Despite the conceptual stance that communities of practice facilitate individual learning, the scientific literature does not offer much evidence for this. Known factors associated with the effectiveness of communities of practice – such as collaboration, psychological safety within the community, and commitment to the community – have been studied in cross-sectional qualitative designs. However, no studies to date have used a quantitative predictive design. The objective of this study is to assess how members of a community of practice perceive interactions among themselves and determine the extent to which these interactions predict self-assessed learning over time. Methods Data was collected using validated questionnaires from six communities of practice (N = 83) in four waves of measures over the course of 36 months and was analysed by means of General Estimating Equations. This allowed to build a longitudinal model of the associations between perceptions of collaboration, psychological safety within the community, commitment to the community and self-assessed learning over time. Results Perception of collaboration in the community of practice, a personal sense of psychological safety and a commitment to the community of practice are predictors longitudinally associated with self-assessed learning. Conclusions In terms of theory, conceptual links can be made between intensity of collaboration and learning over time in the context of a community of practice. Recent work on psychological safety suggests that it is still unclear whether psychological safety acts as a direct enhancer of learning or as a remover of barriers to learning. This study’s longitudinal results suggest that psychological safety may enhance how and to what extent professionals feel they learn over time. Commitment towards the community of practice is a strong predictor of learning over time, which hints at differential effects of affective, normative and continuance commitment. Communities of practice can therefore apply these findings by making collaboration, psychological safety, commitment and learning regular reflexive topics of discussion.

Background & Aims: Liver sinusoidal obstruction syndrome (SOS) is a well-established complication of myeloablative conditioning regimens used in hematopoietic stem cell transplantation. Hepatic venous pressure gradient (HVPG) >10 mmHg was described as an accurate diagnostic tool for SOS in the 1990s. However, epidemiology and presentation of SOS have dramatically changed. Moreover, elementary histological lesions influencing HVPG are unknown. Methods: We retrospectively analyzed the charts of all patients who underwent transjugular liver biopsy with HVPG measurement for a clinical suspicion of SOS at our center. Two expert pathologists unaware of the presence or absence of SOS reviewed all liver samples and graded elementary histological lesions according to a semi-quantitative scoring defined a priori. Results: Out of the 77 included patients, the 30 patients with SOS had higher HVPG than the 47 patients without SOS (median 14 mmHg [IQR 10-18], vs. 6 mmHg [3-9], respectively p 10 mmHg had a specificity of 78% and a positive predictive value of 66% for the diagnosis of SOS. However, almost 40% of the patients with SOS had an HVPG ≤10 mmHg. HVPG correlated with sinusoidal congestion (r = 0.57; p = 0.001) and hepatocyte necrosis (r = 0.42; p = 0.02), but not with other lesions. Conclusion: Even though HVPG is higher in patients with SOS, low HVPG values do not rule out SOS. Thus, HVPG cannot be used alone, and should be combined with transjugular liver biopsy, for the diagnosis of SOS. Lay summary: Hepatic venous pressure gradient >10 mmHg has been described as an accurate tool for the diagnosis of liver sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. This study shows that the sensitivity and specificity of hepatic venous pressure gradient measurement for sinusoidal obstruction syndrome are insufficient, so that liver pressure measurement should be combined with a liver biopsy in this setting.

Abstract Background The successful combination of interprofessional collaboration in multidisciplinary teams with patient-centered care is necessary when it comes to delivering complex mental health services. Yet collaboration is challenging and patient-centered care is intricate to manage. This study examines correlates of patient-centered care such as team adaptivity and proactivity, collaboration, belief in interprofessional collaboration and informational role self-efficacy in multidisciplinary mental health teams. Method A cross-sectional multilevel survey design was used, based on self-administered bilingual validated questionnaires. Participants (N=314) were mental health professionals and managers working in public primary care or specialized mental health services, in inpatient or outpatient settings. Results This study showed that belief in interprofessional collaboration’s relationship with patient-centered perceptions is increased in teams with high collaboration. Collaboration is also found as a mediator, representing a process by which team adaptive and proactive behaviors are transformed into positive patient-centered perceptions. Conclusions Our results were in line with recent studies on team processes establishing that collaboration is a key component in multilevel examinations of predictors of patient-centered care. In terms of practice, our study showed that multidisciplinary teams should know that working hard on collaboration is an answer to the complexity of patient-centered care. Collaboration is related to the teams’ ability to respond to its challenges. It is also related to individuals’ beliefs central to the delivery of interprofessional care.

ObjectiveThe psychological antecedents of the intention to open the windows at home were explored through the Theory of Planned Behavior (TPB), supplemented with Habits regarding the behavior and contextual factors.DesignA four-treatment design compared the effect of an exposure to a recommendation about home ventilation and the effect of one’s own awareness odors (negative vs. positive) as a manipulated variable. Two quasi-experimental online surveys were conducted. A student sample (Study 1; N = 159) was replicated with a general population sample (Study 2; N = 338).ResultsMultiple hierarchical regression models were conducted (3 for Study 1; 3 for Study 2). The extended TPB model provided stable predictors explaining around sixty percent of variance. Attitude and Habits were the main predictors of window openings, Perceived Behavioral control as a secondary predictor. Perceived Behavioral Control contributed significatively with a negative interaction with Attitudes. Odor awareness decreased Intention to manually ventilate. No effect of recommendation was observed.DiscussionThe results filled a gap in the literature about the willingness to manually ventilate at home and efficacy of a recommendation. Practical implications argue that beyond a generic recommendation, effective messages need to be tailored regarding the determinants of willingness to open the windows.

Des universités offrent des cours d’éducation à la collaboration interprofessionnelle en sciences de la santé et, pour faire face aux défis de synchronisation des horaires, de cloisonnement et de communication, plusieurs sont dispensés en mode hybride. Cet article s’intéresse à l’analyse de la qualité métrique d’un questionnaire utilisé en contexte où des équipes interprofessionnelles ont collaboré en ligne et en présentiel dans le cadre d’un cours universitaire hybride en sciences de la santé. Initialement, ce questionnaire a été conçu pour des personnes du monde du travail dans le but d’évaluer les composantes de la collaboration (communication, synchronisation et coordinations explicite et implicite) mobilisées en présentiel. Les résultats des analyses factorielles confirmatoires de second ordre appuient les qualités métriques du questionnaire original. La collaboration en ligne et en présentiel pourraient être mesurées à l’aide de ce questionnaire dans un cours universitaire hybride. L’étude mobilise des connaissances sur l’évaluation de la collaboration, une voie scientifique peu connue à ce jour.

Universities are offering hybrid interprofessional health sciences collaboration education courses to address the challenges of schedule synchronization, silos, and communication. This article focuses on analyzing the psychometric quality of a questionnaire used in a setting where interprofessional teams collaborated online and face-to-face in a hybrid university health sciences course. This questionnaire was originally designed for people in the working world in order to assess the constructs of collaboration (communication, synchronization and explicit and implicit coordination) mobilized in the face-to-face setting. The results of the second order confirmatory factor analyses support its use in an academic context and support the metric qualities of the original questionnaire. Online and face-to-face collaboration could be measured using this questionnaire in a hybrid university pedagogical context. The study mobilizes knowledge about the evaluation of collaboration, an avenue that little research has taken to date.

Detecting fatigue during training sessions would help riders and trainers to optimize their training. It has been shown that fatigue could affect movement patterns. Inertial measurement units (IMUs) are wearable sensors that measure linear accelerations and angular velocities, and can also provide orientation estimates. These sensors offer the possibility of a non-invasive and continuous monitoring of locomotion during training sessions. However, the indicators extracted from IMUs and their ability to show these locomotion changes are not known. The present study aims at defining which kinematic variables and indicators could highlight locomotion changes during a training session expected to be particularly demanding for the horses. Heart rate and lactatemia were measured to attest for the horse’s fatigue following the training session. Indicators derived from acceleration, angular velocities, and orientation estimates obtained from nine IMUs placed on 10 high-level dressage horses were compared before and after a training session using a non-parametric Wilcoxon paired test. These indicators were correlation coefficients (CC) and root mean square deviations (RMSD) comparing gait cycle kinematics measured before and after the training session and also movement smoothness estimates (SPARC, LDLJ). Heart rate and lactatemia measures did not attest to a significant physiological fatigue. However, the statistics show an effect of the training session (p < 0.05) on many CC and RMSD computed on the kinematic variables, indicating a change in the locomotion with the training session as well as on SPARCs indicators (p < 0.05), and revealing here a change in the movement smoothness both in canter and trot. IMUs seem then to be able to track locomotion pattern modifications due to training. Future research should be conducted to be able to fully attribute the modifications of these indicators to fatigue.