International Consortium Research Articles

Excess all-cause mortality in 21 countries during 2022: COVID-19 impact by C-MOR project

Abstract National published COVID-19 mortality estimates do not fully encompass the extent of the pandemic’s impact on mortality. To address this challenge, calculating excess all-cause mortality at the national level is important. Our focus was on understanding total weekly excess mortality for 2022, by analysing mortality data across 2020-2022, from 21 countries participating in the international consortium (C-MOR), which provided data for examination. Excess mortality was calculated by comparing the weekly 2022 age-standardized mortality rates per 100,000 population against a baseline mortality, estimated using historical data from 2015-2019. Excess cumulative mortality for 2022 was found in all 21 countries. The excess mortality for the total population varied between 8.6 and 116.2, with the minimum excess belonging to Peru and the maximum to Georgia. Australia, Austria, Cyprus, Denmark, Estonia, Georgia, Greece, Israel, and Norway showed a higher excess in 2022 than in 2020, while Australia, Austria, Cyprus, Denmark, Israel, Italy, Norway, Spain, and Sweden also showed a higher excess in 2022 than in 2021. Mauritius showed a significant excess mortality for the first time in 2022. For all countries, but Australia, the % of COVID-19 deaths out of all deaths decreased in 2022 compared to 2021. Contrary to the ‘harvesting effect’, which would expect a decline in mortality rates post-pandemic, our results underscore a sustained excess mortality throughout 2022. The 2022 excess deaths are mainly non-COVID-related, stemming from broader pandemic impacts on healthcare systems and other factors. Conversely, in Australia, international boarders reopened in 2022, resulting in the first community-wide transmission and a substantial rise in excess deaths. Our study reveals nuanced excess mortality dynamics post-vaccination, providing crucial insights for policymakers and stressing the necessity of continued vigilance and adaptive strategies against COVID-19’s diverse impacts. Key messages • All countries investigated experienced continued all-cause excess mortality during 2022, compared to pre-pandemic years. For most, excess mortality in 2022 was higher than in 2021 and 2020. • For all countries, except Australia, the contribution of COVID-19 deaths to the mortality estimates in 2022 is decreased, highlighting the impact of indirect pandemic related effects on mortality.

The state-of-the-art and barriers for the adoption of personalised prevention in Europe and beyond

Abstract Personalized prevention is a priority of the European Commission’s research agenda, exemplified by the EU-funded project ‘a PeRsonalised Prevention roadmap for the future HEalThcare’ (PROPHET), a coordination and support action of the International Consortium for Personalized Medicine. It aims to bolster health systems in implementing innovative, sustainable, and high-quality personalized strategies to prevent chronic diseases. In this context, a scoping review was conducted to map personalized preventive approaches (PPA) for chronic diseases and obstacles to their adoption worldwide. The review followed the Arksey-O’Malley guidelines and was conducted from January 2017 to December 2023, on PubMed, Web of Science, Scopus, and grey literature. Eligible studies were primary reports and guidelines, while for the barriers to their adoption we included literature reviews. We included 120 documents on approaches and 34 reviews on barriers. Among the former, 251 PPA were identified: 69% on cancer, 21% on cardiovascular diseases, and 10% on neurological, psychiatric, and metabolic diseases. Furthermore, 27% were on primary prevention, using omic biomarkers to predict disease risk and guide preventive strategies; 27% on secondary prevention, using genomics to guide screening programs; 46% on tertiary prevention, using pharmacogenomics or targeted therapies to prevent disease complications. Among the 34 reviews on barriers, the majority were about the lack of clinical utility evidence and research needs, ethical and legal issues, and limited knowledge among health professionals, citizens, and patients. The majority of the barriers (76%) were referred to primary and secondary prevention, consistent with the low rates of existing approaches in these areas. Ongoing efforts show promise for tailoring prevention strategies, but further research and integration are needed to maximize their potential in improving population health and reducing chronic disease burdens on health systems.

Prognostic nomograms for young breast cancer: A retrospective study based on the SEER and METABRIC databases.

Young breast cancer (YBC) is a subset of breast cancer that is often more aggressive, but less is known about its prognosis. In this study, we aimed to generate nomograms to predict the overall survival (OS) and breast cancer-specific survival (BCSS) of YBC patients. Data of women diagnosed with YBC between 2010 and 2020 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly allocated into a training cohort (n = 15,227) and internal validation cohort (n = 6,526) at a 7:3 ratio. With the Cox regression models, significant prognostic factors were identified and used to construct 3-, 5-, and 10-year nomograms of OS and BCSS. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used as an external validation cohort (n = 90). We constructed nomograms incorporating 10 prognostic factors for OS and BCSS. These nomograms demonstrated strong predictive accuracy for OS and BCSS in the training cohort, with C-indexes of 0.806 and 0.813, respectively. The calibration curves verified that the nomograms have good prediction accuracy. Decision curve analysis demonstrated their practical clinical value for predicting YBC patient survival rates. Additionally, we provided dynamic nomograms to improve the operability of the results. The risk stratification ability assessment also showed that the OS and BCSS rates of the low-risk group were significantly better than those of the high-risk group. Here, we generated and validated more comprehensive and accurate OS and BCSS nomograms than models previously developed for YBC. These nomograms can help clinicians evaluate patient prognosis and make clinical decisions.

EnteroBase in 2025: exploring the genomic epidemiology of bacterial pathogens.

This paper presents an update on the content, accessibility and analytical tools of the EnteroBase platform for web-based pathogen genome analysis. EnteroBase provides manually curated databases of genome sequence data and associated metadata from currently>1.1 million bacterial isolates, more recently including Streptococcus spp. and Mycobacterium tuberculosis, in addition to Salmonella,Escherichia/Shigella,Clostridioides,Vibrio,Helicobacter,YersiniaandMoraxella. We have implemented the genome-based detection of antimicrobial resistance determinants and the new bubble plot graphical tool for visualizing bacterial genomic population structures, based on pre-computed hierarchical clusters. Access to data and analysis tools is provided through an enhanced graphical user interface and a new application programming interface (RESTful API). EnteroBase is now being developed and operated by an international consortium, to accelerate the development of the platform and ensure the longevity of the resources built. EnteroBase can be accessed at https://enterobase.warwick.ac.uk as well as https://enterobase.dsmz.de.

Cuerpos, territorio y biopolítica plebeya

The current conditions of the advance of neoliberalism in Latin America have propitiated policys and legislations that privilege the subtraction of natural resources by private national or international consortia. In so doing, they have favored the environmental deterioration of large regions and the dispossession of rural communities, mainly indigenous, that inhabit them. The existence of a crisis that occurred within this framework evidenced the risks of an extractive model, especially from the Covid-19 pandemic. This has led to the evolution of social demands in some movements, such as those that have been given in defense of the territory, wich currently tend to put the protection of life in the foreground, not just human, but nature itself. Based on some experiences of members of indigenous peoples, as a result of observation, interviews carried out, mainly with some women and research on the Internet, this article proposes to think about these struggles that lead to the political arena a field of dispute around to the expansion or constriction of life forms. From this context it is possible to introduce a reflection on biopolitics, beyond biopower, as Foucault proposed it. It is in this sense that I suggest the notion of plebeian biopolitic.

IPNA consensus definitions for clinical trial outcomes in steroid-resistant nephrotic syndrome.

Assessment of the true impact of therapeutic interventions is a challenge in the absence of universal, standardized definitions for clinical trial endpoints in children with kidney diseases. Steroid-resistant nephrotic syndrome (SRNS) is a difficult kidney disease to treat, with unremitting disease progressing to kidney failure. Currently, available therapies result in suboptimal cure rates. Clinical trials with innovative, targeted treatments will likely be conducted for this disease in the foreseeable future. An international consortium of the IPNA Best Practices and Standards Committee and the Pediatric Nephrology Expert Group of the conect4children (c4c) network developed through consensus, standardized, internationally acceptable definitions for trial outcomes for SRNS. The endpoint definitions were formulated for use with urine protein to creatinine ratios and estimated glomerular filtration rates. Definitions of complete remission, partial remission, non-remission of disease, reduction in proteinuria, kidney disease progression, kidney failure, and composite kidney outcome were refined using an iterative process until a consensus was achieved.

Roles of different organizations in implementing patient-reported measures in routine maternity care in Finland

BackgroundThe integration of patient-centered care (PCC) and value-based healthcare (VBHC) principles, emphasizing personalized, responsive care and cost efficiency, is crucial in modern healthcare. Despite advocation from the International Consortium for Health Outcomes Measurement (ICHOM) for the global adoption of these principles through patient-reported measures (PRMs), their implementation, especially the pregnancy and childbirth (PCB) set, remains limited in maternity care. This study focuses on understanding the optimal organizational entity for integrating standard ICHOM-PCB-PRMs into routine maternity care in Finland. It aims to clarify the distribution of tasks among stakeholders and gather Finnish maternity healthcare professionals’ perspectives on organizational responsibility in PRM collection. The emphasis was on identifying the optimal organizational framework for managing PRMs in maternity care.ResultsA total of 66 maternity healthcare professionals participated in the study, reaching a consensus that public maternity care centers in Finland should be the primary entity responsible for managing PRMs in the maternity sector. Key aspects such as confidence with the role as a mother, maternal confidence with breastfeeding, and satisfaction with the result of care were identified as crucial and should be inquired about in both public maternity care centers and hospital maternity wards. The findings highlight the importance of comprehensive and consistent attention to these PRMs across public maternity care centers and hospital maternity settings to ensure holistic and effective maternal care.ConclusionsThe study highlights the central role of public maternity care centers in the collection and management of PRMs within Finnish maternity care, as agreed upon by the professional consensus. It underscores the importance of a consistent and holistic approach to PRM inquiry across different care settings to enhance the quality and effectiveness of maternity care. This finding is crucial for policymakers and healthcare practitioners, suggesting that reinforcing the collaborative efforts between public maternity care centers and hospital maternity wards is vital for a patient-centric, efficient healthcare system. Aligning with PCC and VBHC principles, this approach aims to improve healthcare outcomes for pregnant and postpartum women in Finland, emphasizing the need for a unified strategy in managing maternity care.

Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts

Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up. The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024. Incident stroke. The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores. The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition. In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.

The Multi-Country Multi-City Collaborative Research Network: An international research consortium investigating environment, climate, and health.

Research on the health risks of environmental factors and climate change requires epidemiological evidence on associated health risks at a global scale. Multi-center studies offer an excellent framework for this purpose, but they present various methodological and logistical problems. This contribution illustrates the experience of the Multi-Country Multi-City Collaborative Research Network, an international collaboration working on a global research program on the associations between environmental stressors, climate, and health in a multi-center setting. The article illustrates the collaborative scheme based on mutual contribution and data and method sharing, describes the collection of a huge multi-location database, summarizes published research findings and future plans, and discusses advantages and limitations. The Multi-Country Multi-City represents an example of a collaborative research framework that has greatly contributed to advance knowledge on the health impacts of climate change and other environmental factors and can be replicated to address other research questions across various research fields.

Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes.

The WHO and International Consensus Classification 2022 classifications of myelodysplastic syndromes enhance diagnostic precision and refine decision-making processes in these diseases. However, some discrepancies still exist and potentially cause inconsistency in their adoption in a clinical setting. We adopted a data-driven approach to provide a harmonisation between these two classification systems. We investigated the importance of genomic features and their effect on the cluster assignment process to define harmonised entity labels. A panel of expert haematologists, haematopathologists, and data scientists who are members of the International Consortium for Myelodysplastic Syndromes was formed and a modified Delphi consensus process was adopted to harmonise morphologically defined categories without a distinct genomic profile. The panel held regular online meetings and participated in a two-round survey using an online voting tool. We identified nine clusters with distinct genomic features. The cluster of highest hierarchical importance was characterised by biallelic TP53 inactivation. Cluster assignment was irrespective of blast count. Individuals with monoallelic TP53 inactivation were assigned to other clusters. Hierarchically, the second most important group included myelodysplastic syndromes with del(5q). Isolated del(5q) and less than 5% of blast cells in the bone marrow were the most relevant label-defining features. The third most important cluster included myelodysplastic syndromes with mutated SF3B1. The absence of isolated del(5q), del(7q)/-7, abn3q26.2, complex karyotype, RUNX1 mutations, or biallelic TP53 were the basis for a harmonised label of this category. Morphologically defined myelodysplastic syndrome entities showed large genomic heterogeneity that was not efficiently captured by single-lineage versus multilineage dysplasia, marrow blasts, hypocellularity, or fibrosis. We investigated the biological continuum between myelodysplastic syndromes with more than 10% bone marrow blasts and acute myeloid leukaemia, and found only a partial overlap in genetic features. After the survey, myelodysplastic syndromes with low blasts (ie, less than 5%) and myelodysplastic syndromes with increased blasts (ie, 5% or more) were recognised as disease entities. Our data-driven approach can efficiently harmonise current classifications of myelodysplastic syndromes and provide a reference for patient management in a real-world setting.

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study

BackgroundElevated mammographic density (MD) for a woman’s age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD).MethodsICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35–85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest.ResultsAmong 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: − 0.05, 95% confidence interval (CI): − 0.07, − 0.03) and √DA (β: − 0.08, 95% CI: − 0.12, − 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: − 0.06, 95% CI: − 0.11, − 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD.ConclusionsAssociations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10-4), cataract (p = 3 × 10-3), and T1D (p = 1 × 10-3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10-4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10-3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.

Developing Standard Sets of Indicators for Patient-Centered Outcome Measures

The article describes how working groups of medical specialists led by the International Consortium for Health Outcomes Measurement (ICHOM) develop standard sets of indicators for patient-centered outcome measures. The main stages of working groups’ activity, methods, and criteria for including indicators were defined. The study showed that outcomes are comparable across countries since standard sets of indicators can be used by healthcare organizations all over the world, regardless of the healthcare model. While it is confirmed that the data obtained using PROM questionnaires are valid and reliable, it is recommended, based on the literature review, to fine-tune the standard sets of indicators for some nosologies to the features of the local healthcare system.

Circulating tryptophan–kynurenine pathway metabolites are associated with all‐cause mortality among patients with stage I–III colorectal cancer

AbstractAlterations within the tryptophan–kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan–kynurenine pathway metabolites and all‐cause mortality among CRC patients. This study utilizes data from 2102 stage I–III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3‐hydroxykynurenine (HK), xanthurenic acid (XA), 3‐hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography–tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above‐mentioned metabolites with all‐cause mortality, adjusted for potential confounders. During a median follow‐up of 3.2 years (interquartile range: 2.2–4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all‐cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine‐to‐tryptophan ratio, a marker of cell‐mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan–kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.

Defining an ageing-related pathology, disease or syndrome: International Consensus Statement.

Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.

Review article: Recommendations for detection, assessment and management of suspected drug‐induced liver injury during clinical trials in oncology patients

SummaryBackgroundDrug‐induced liver injury (DILI) is a major concern for oncology drugs in clinical practice and under development. Monitoring cancer patients for hepatotoxicity is challenging as these patients may have abnormal liver tests pre‐treatment or on‐study for many reasons including liver injury due to past oncology treatments, hepatic metastases, medical co‐morbidities such as heart failure, and concomitant medications. At present, there are no regulatory guidelines or position papers that systematically address best practices pertaining to DILI detection, assessment and management in oncology patients.AimsThe goals of this review are (1) to examine and interpret the available evidence and (2) to make recommendations for detection, monitoring, adjudication, and management of suspected hepatocellular DILI during oncology clinical trials.MethodsThis manuscript was developed by the IQ Consortium (International Consortium for Innovation and Quality in pharmaceutical development) DILI Initiative that consists of members from 17 pharmaceutical companies, in collaboration with academic and regulatory DILI experts. The manuscript is based on extensive literature review, expert interpretation of the literature, and several rounds of consensus discussions.ResultsThis review highlights recommendations for patient eligibility for clinical trials with or without primary/metastatic liver involvement, as well as changes in liver tests that should trigger increased monitoring and/or discontinuation of study drug. Guidance regarding causality assessment for suspected DILI events, rechallenge and dose‐modification is provided.ConclusionsThis review brings together evidence‐based recommendations and expert opinion to provide the first dedicated consensus for best practices in detection, assessment, and management of DILI in oncology clinical trials.

Sex differences in the outcome of critically Ill patients with COVID-19 - An international multicenter critical care consortium study

BackgroundSex differences in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility, illness severity, and hospital course are widely acknowledged. The effects of sex on outcomes experienced by patients with severe Coronavirus Disease 2019 (COVID-19) admitted to the intensive care unit (ICU) remains unknown. ObjectivesTo determine the effects of sex on ICU mortality in patients with COVID-19 MethodsThis retrospective analysis of an international multi-center prospective observational database included adults admitted to ICU for treatment of acute COVID-19 between 1st January 2020 and 30th June 2022. The primary outcome was ICU mortality. Multivariable Cox regression was used to ascertain the hazard of death (Hazard Ratio=HR) adjusted for pre-selected covariates. The secondary outcome was sex differences in complications of COVID-19 during hospital stay. ResultsOverall, 10,259 patients (3,314 females, 6,945 males) were included with a median age of 60 (interquartile range [IQR]=49–68) and 59 (IQR=49–67) years, respectively. Baseline characteristics were similar between sexes. More females were non-smokers (65% vs. 44 %, p < 0.01) and obese (39% vs. 30 %, p < 0.01), compared to males. Also, males received greater ICU intervention (mechanical ventilation, prone ventilation, vasopressors, and tracheostomy) than females. Males had a greater hazard of death (compared to females, HR=1.14; 95 % CI=1.02–1.26). Adjustment for complications during hospital stay did not alter the hazard of death (HR=1.16; 95 % CI=1.05–1.28). Males had a significantly elevated hazard of death among patients who received ECMO (HR=1.24; 95 % CI=1.01–1.53). Male sex was associated with cardiac arrest (adjusted OR [aOR]=1.37; 95 % CI=1.16–1.62) and PE (aOR=1.28; 95 % CI=1.06–1.55). ConclusionAmong patients admitted to ICU for severe COVID-19, males experienced higher severity of illness and more frequent intervention than females. Ultimately, the hazard of death was moderately elevated in males compared to females despite greater PE and cardiac arrest.

The experience sampling methodology as a digital clinical tool for more person-centered mental health care: an implementation research agenda.

This position paper by the international IMMERSE consortium reviews the evidence of a digital mental health solution based on Experience Sampling Methodology (ESM) for advancing person-centered mental health care and outlines a research agenda for implementing innovative digital mental health tools into routine clinical practice. ESM is a structured diary technique recording real-time self-report data about the current mental state using a mobile application. We will review how ESM may contribute to (1) service user engagement and empowerment, (2) self-management and recovery, (3) goal direction in clinical assessment and management of care, and (4) shared decision-making. However, despite the evidence demonstrating the value of ESM-based approaches in enhancing person-centered mental health care, it is hardly integrated into clinical practice. Therefore, we propose a global research agenda for implementing ESM in routine mental health care addressing six key challenges: (1) the motivation and ability of service users to adhere to the ESM monitoring, reporting and feedback, (2) the motivation and competence of clinicians in routine healthcare delivery settings to integrate ESM in the workflow, (3) the technical requirements and (4) governance requirements for integrating these data in the clinical workflow, (5) the financial and competence related resources related to IT-infrastructure and clinician time, and (6) implementation studies that build the evidence-base. While focused on ESM, the research agenda holds broader implications for implementing digital innovations in mental health. This paper calls for a shift in focus from developing new digital interventions to overcoming implementation barriers, essential for achieving a true transformation toward person-centered care in mental health.

AARS Online: A collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases.

The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non-experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS.

Defining an Ageing-Related Pathology, Disease or Syndrome: International Consensus Statement.

Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased healthspan. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand, and meet the healthcare, workforce, wellbeing, and socioeconomic needs of ageing populations, while supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19 th , 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were: Develops and/or progresses with increasing chronological age.Should be associated with, or contribute to, functional decline, or an increased susceptibility to functional decline.Evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.