Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype.

BACKGROUND: The aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. MATERIAL AND METHODS: We retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. RESULTS: From 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (-39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16-7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08-17.42]; p = 0.04). CONCLUSIONS: Our study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

A methodological review of the high-dimensional propensity score in comparative-effectiveness and safety-of-interventions research finds incomplete reporting relative to algorithm development and robustness.

OBJECTIVES: The use of secondary databases has become popular for evaluating the effectiveness and safety of interventions in real-life settings. However, the absence of important confounders in these databases is challenging. To address this issue, the high-dimensional propensity score (hdPS) algorithm was developed in 2009. This algorithm uses proxy variables for mitigating confounding by combining information available across several healthcare dimensions. This study assessed the methodology and reporting of the hdPS in comparative effectiveness and safety research. STUDY DESIGN AND SETTING: In this methodological review, we searched PubMed and Google Scholar from July 2009 to May 2022 for studies that used the hdPS for evaluating the effectiveness or safety of healthcare interventions. Two reviewers independently extracted study characteristics and assessed how the hdPS was applied and reported. Risk of bias was evaluated with the Rrisk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. RESULTS: In total, 136 studies met the inclusion criteria; the median publication year was 2018 (Q1-Q3 2016-2020). The studies included 192 datasets, mostly North American databases (n = 132, 69%). The hdPS was used in primary analysis in 120 studies (88%). Dimensions were defined in 101 studies (74%), with a median of 5 (Q1-Q3 4-6) dimensions included. A median of 500 (Q1-Q3 200-500) empirically identified covariates were selected. Regarding hdPS reporting, only 11 studies (8%) reported all recommended items. Most studies (n = 81, 60%) had a moderate overall risk of bias. CONCLUSION: There is room for improvement in the reporting of hdPS studies, especially regarding the transparency of methodological choices that underpin the construction of the hdPS.

Screening of triploid banana population under natural and controlled black sigatoka disease for genomic selection.

The black sigatoka disease (BSD) is the most important foliar threat in banana production and breeding efforts against it should take advantage of genomic selection (GS) that has become one of the most explored tools to increase genetic gain, save time and reduce selection costs. In order to evaluate the potential of GS in banana for BSD, 210 triploid accessions were obtained from the African Banana and Plantain Research Center (CARBAP) to constitute a training population (TP). The variability in the population was assessed at the phenotypic level using BSD- and agronomic-related traits and at the molecular level using Single Nucleotide Polymorphism (SNPs). The analysis of variance showed a significant difference between accessions for almost all traits measured, while at the genomic group level; there was no significant difference for BSD-related traits. The Index of Non spotted leave among accessions ranged from 0.11 to 0.8. The accessions screening in controlled conditions confirmed the susceptibility of all genomic groups to BSD. The principal components analysis with phenotypic data revealed no clear diversity partition of the population. However, the structure analysis and the hierarchical clustering analysis with SNPs grouped the population into four (4) clusters and two (2) sub-populations respectively. The field and laboratory screening of the banana genomic selection TP confirmed that all genomic groups are susceptible to BSD but did not reveal any genetic structure while SNPs markers exhibited clear genetic structure and provided useful information in the perspective of applying genomic selection.

Prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis of non-pharmacological interventions.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. METHODS: We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS: We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I2 = 0%; Phet = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I2 = 23%; Phet = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I2 = 53%; Phet < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; Phet = 0.67; I2 = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; Phet = 0.25; I2 = 26%). CONCLUSIONS: Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.

Delaying anterior cruciate ligament reconstruction increases the rate and severity of medial chondral injuries.

Aims: The aim of this study was to evaluate the association between chondral injury and interval from anterior cruciate ligament (ACL) tear to surgical reconstruction (ACLr). Methods: Between January 2012 and January 2022, 1,840 consecutive ACLrs were performed and included in a single-centre retrospective cohort. Exclusion criteria were partial tears, multiligament knee injuries, prior ipsilateral knee surgery, concomitant unicompartmental knee arthroplasty or high tibial osteotomy, ACL agenesis, and unknown date of tear. A total of 1,317 patients were included in the final analysis, with a median age of 29 years (interquartile range (IQR) 23 to 38). The median preoperative Tegner Activity Score (TAS) was 6 (IQR 6 to 7). Patients were categorized into four groups according to the delay to ACLr: < three months (427; 32%), three to six months (388; 29%), > six to 12 months (248; 19%), and > 12 months (254; 19%). Chondral injury was assessed during arthroscopy using the International Cartilage Regeneration and Joint Preservation Society classification, and its association with delay to ACLr was analyzed using multivariable analysis. Results: In the medial compartment, delaying ACLr for more than 12 months was associated with an increased rate (odds ratio (OR) 1.93 (95% confidence interval (CI) 1.27 to 2.95); p = 0.002) and severity (OR 1.23 (95% CI 1.08 to 1.40); p = 0.002) of chondral injuries, compared with < three months, with no association in patients aged > 50 years old. No association was found for shorter delays, but the overall dose-effect analysis was significant for the rate (p = 0.015) and severity (p = 0.026) of medial chondral injuries. Increased TAS was associated with a significantly reduced rate (OR 0.88 (95% CI 0.78 to 0.99); p = 0.036) and severity (OR 0.96 (95% CI 0.92 to 0.99); p = 0.017) of medial chondral injuries. In the lateral compartment, no association was found between delay and chondral injuries. Conclusion: Delay was associated with an increased rate and severity of medial chondral injuries in a dose-effect fashion, in particular for delays > 12 months. Younger patients seem to be at higher risk of chondral injury when delaying surgery. The timing of ACLr should be optimally reduced in this population.

Shared pedigree relationships and transmission of unreduced gametes in cultivated banana.

BACKGROUND AND AIMS: Cultivated bananas resulted from inter(sub)specific hybridizations involving Musa species and subspecies (M. acuminata subspecies, M. schizocarpa, M. balbisiana) and the subsequent selection, centuries ago, of hybrids with parthenocarpic, seedless fruits. Cultivars have low fertility and are vegetatively propagated, forming groups of somaclones. Relatively few of them, mainly triploids, are grown on a large scale and characterization of their parental relationships may be useful for breeding strategies. Here we investigate parental relationships and gamete-type contributions among diploid and polyploid banana cultivars. METHODS: We used SNP genotyping data from whole-genome sequencing of 178 banana individuals, including 111 cultivars, 55 wild bananas and 12 synthetic F1 hybrids. We analysed the proportion of SNP sites in accordance with direct parentage with a global statistic and along chromosomes for selected individuals. KEY RESULTS: We characterized parentage relationships for 7 diploid cultivars, 11 triploid cultivars and 1 tetraploid cultivar. Results showed that both diploid and triploid cultivars could have contributed gametes to other banana cultivars. Diploids may have contributed 1x or 2x gametes and triploids 1x to 3x gametes. The Mchare diploid cultivar group, nowadays only found in East Africa, was found as parent of two diploid and eight triploid cultivars. In five of its identified triploid offspring, corresponding to main export or locally popular dessert bananas, Mchare contributed a 2x gamete with full genome restitution without recombination. Analyses of remaining haplotypes in these Mchare offspring suggested ancestral pedigree relationships between different interspecific banana cultivars. CONCLUSIONS: The current cultivated banana resulted from different pathways of formation, with implication of recombined or un-recombined unreduced gametes produced by diploid or triploid cultivars. Identification of dessert banana's parents and the types of gametes they contributed should support the design of breeding strategies.

Genetic Mapping, Candidate Gene Identification and Marker Validation for Host Plant Resistance to the Race 4 of Fusarium oxysporum f. sp. cubense Using Musa acuminata ssp. malaccensis.

Fusarium wilt of banana is a devastating disease that has decimated banana production worldwide. Host resistance to Fusarium oxysporum f. sp. Cubense (Foc), the causal agent of this disease, is genetically dissected in this study using two Musa acuminata ssp. Malaccensis segregating populations, segregating for Foc Tropical (TR4) and Subtropical (STR4) race 4 resistance. Marker loci and trait association using 11 SNP-based PCR markers allowed the candidate region to be delimited to a 12.9 cM genetic interval corresponding to a 959 kb region on chromosome 3 of 'DH-Pahang' reference assembly v4. Within this region, there was a cluster of pattern recognition receptors, namely leucine-rich repeat ectodomain containing receptor-like protein kinases, cysteine-rich cell-wall-associated protein kinases, and leaf rust 10 disease-resistance locus receptor-like proteins, positioned in an interspersed arrangement. Their transcript levels were rapidly upregulated in the resistant progenies but not in the susceptible F2 progenies at the onset of infection. This suggests that one or several of these genes may control resistance at this locus. To confirm the segregation of single-gene resistance, we generated an inter-cross between the resistant parent 'Ma850' and a susceptible line 'Ma848', to show that the STR4 resistance co-segregated with marker '28820' at this locus. Finally, an informative SNP marker 29730 allowed the locus-specific resistance to be assessed in a collection of diploid and polyploid banana plants. Of the 60 lines screened, 22 lines were predicted to carry resistance at this locus, including lines known to be TR4-resistant, such as 'Pahang', 'SH-3362', 'SH-3217', 'Ma-ITC0250', and 'DH-Pahang/CIRAD 930'. Additional screening in the International Institute for Tropical Agriculture's collection suggests that the dominant allele is common among the elite 'Matooke' NARITA hybrids, as well as in other triploid or tetraploid hybrids derived from East African highland bananas. Fine mapping and candidate gene identification will allow characterization of molecular mechanisms underlying the TR4 resistance. The markers developed in this study can now aid the marker-assisted selection of TR4 resistance in breeding programs around the world.

Heterogeneity in the definition of delirium in ICUs and association with the intervention effect in randomized controlled trials: a meta-epidemiological study.

PURPOSE: To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used. METHODS: We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported). We conducted a meta-epidemiological analysis to compare intervention effects between trials using or not a validated definition by a two-step method as primary analysis and a multilevel model as secondary analysis. A ratio of odds ratios (ROR) < 1 indicated larger intervention effects in trials using a non-validated definition. RESULTS: Of 149 RCTs (41 meta-analyses), 109 (73.1%) used a validated definition and 40 (26.8%) did not (including 31 [20.8%] not reporting the definition). The primary analysis of 7 meta-analyses (30 RCTs) found no significant difference in intervention effects between trials using a validated definition and the others (ROR = 0.54, 95% CI 0.27-1.08), whereas the secondary multilevel analysis including 12 meta-analyses (67 RCTs) found significantly larger effects for trials using a non-validated versus a validated definition (ROR = 0.36, 95% CI 0.21-0.62). CONCLUSION: The definition of delirium was heterogeneous across RCTs, with one-fifth not reporting how they evaluated delirium. We did not find a significant association with intervention effect in the primary analysis. The secondary analysis including more studies revealed significantly larger intervention effects in trials using a non-validated versus a validated definition.

Identification of a Major QTL-Controlling Resistance to the Subtropical Race 4 of Fusarium oxysporum f. sp. cubense in Musa acuminata ssp. malaccensis.

Vascular wilt caused by the ascomycete fungal pathogen Fusarium oxysporum f. sp. cubense (Foc) is a major constraint of banana production around the world. The virulent race, namely Tropical Race 4, can infect all Cavendish-type banana plants and is now widespread across the globe, causing devastating losses to global banana production. In this study, we characterized Foc Subtropical Race 4 (STR4) resistance in a wild banana relative which, through estimated genome size and ancestry analysis, was confirmed to be Musa acuminata ssp. malaccensis. Using a self-derived F2 population segregating for STR4 resistance, quantitative trait loci sequencing (QTL-seq) was performed on bulks consisting of resistant and susceptible individuals. Changes in SNP index between the bulks revealed a major QTL located on the distal end of the long arm of chromosome 3. Multiple resistance genes are present in this region. Identification of chromosome regions conferring resistance to Foc can facilitate marker assisted selection in breeding programs and paves the way towards identifying genes underpinning resistance.

Analysis of genetic diversity and agronomic variation in banana sub-populations for genomic selection under drought stress in southern Benin.

In the perspective of investigating genomic selection (GS) among Musa genotypes in West and Central Africa, banana accessions were phenotyped under natural drought stress in Benin and genotyped using genotyping by sequencing. Sixty-one (61) accessions grouped into three major genomic groups AAA, AAB and ABB and those without genomic affiliation information were used. Variation within the population was determined by phenotypic variables while population structure and clustering analysis were carried out to understand the genetic diversity at the molecular level. Among the genomic groups evaluated, the group AAB showed the best performance for fruit weight at maturity, (3.41 ± 1.99 kg) and for plant height (198.46 ± 12.66 cm). At the accession level, HD 117 S1 and NIA 27 showed the best plant height (263.16 ± 20.98 cm) and the best fruit weight at maturity (9.43 ± 0.0 kg) respectively. Phenotypic data did not reveal clear genetic diversity among accessions; however, the genetic diversity was conspicuous at the molecular level using 5000 markers. The affiliations of local accessions in genomic groups were determined for the first time based on the phenotypic and molecular data obtained in this study. The knowledge generated allows the possibility to apply GS in banana.

Days Spent at Home and Mortality After Critical Illness: A Cluster Analysis Using Nationwide Data.

BACKGROUND: Beyond the question of short-term survival, days spent at home could be considered a patient-centered outcome in critical care trials. RESEARCH QUESTION: What are the days spent at home and health care trajectories during the year after surviving critical illness? STUDY DESIGN AND METHODS: Data were extracted on adult survivors spending at least 2 nights in a French ICU during 2018 who were treated with invasive mechanical ventilation or vasopressors or inotropes. Trauma, burn, organ transplant, stroke, and neurosurgical patients were excluded. Stays at home, death, and hospitalizations were reported before and after ICU stay, using state sequence analysis. An unsupervised clustering method was performed to identify cohorts based on post-ICU trajectories. RESULTS: Of 77,132 ICU survivors, 89% returned home. In the year after discharge, these patients spent a median of 330 (interquartile range [IQR], 283-349) days at home. At 1 year, 77% of patients were still at home and 17% had died. Fifty-one percent had been re-hospitalized, and 10% required a further ICU admission. Forty-eight percent used rehabilitation facilities, and 5.7%, hospital at home. Three clusters of patients with distinct post-ICU trajectories were identified. Patients in cluster 1 (68% of total) survived and spent most of the year at home (338 [323-354] days). Patients in cluster 2 (18%) had more complex trajectories, but most could return home (91%), spending 242 (174-277) days at home. Patients in cluster 3 (14%) died, with only 37% returning home for 45 (15-90) days. INTERPRETATION: Many patients had complex health care trajectories after surviving critical illness. Wide variations in the ability to return home after ICU discharge were observed between clusters, which represents an important patient-centered outcome.

Interspecific introgression patterns reveal the origins of worldwide cultivated bananas in New Guinea.

Hybridizations between Musa species and subspecies, enabled by their transport via human migration, were proposed to have played an important role in banana domestication. We exploited sequencing data of 226 Musaceae accessions, including wild and cultivated accessions, to characterize the inter(sub)specific hybridization pattern that gave rise to cultivated bananas. We identified 11 genetic pools that contributed to cultivars, including two contributors of unknown origin. Informative alleles for each of these genetic pools were pinpointed and used to obtain genome ancestry mosaics of accessions. Diploid and triploid cultivars had genome mosaics involving three up to possibly seven contributors. The simplest mosaics were found for some diploid cultivars from New Guinea, combining three contributors, i.e., banksii and zebrina representing Musa acuminata subspecies and, more unexpectedly, the New Guinean species Musa schizocarpa. Breakpoints of M. schizocarpa introgressions were found to be conserved between New Guinea cultivars and the other analyzed diploid and triploid cultivars. This suggests that plants bearing these M. schizocarpa introgressions were transported from New Guinea and gave rise to currently cultivated bananas. Many cultivars showed contrasted mosaics with predominant ancestry from their geographical origin across Southeast Asia to New Guinea. This revealed that further diversification occurred in different Southeast Asian regions through hybridization with other Musa (sub)species, including two unknown ancestors that we propose to be M. acuminata ssp. halabanensis and a yet to be characterized M. acuminata subspecies. These results highlighted a dynamic crop formation process that was initiated in New Guinea, with subsequent diversification throughout Southeast Asia.

The banana genome hub: a community database for genomics in the Musaceae.

The Banana Genome Hub provides centralized access for genome assemblies, annotations, and the extensive related omics resources available for bananas and banana relatives. A series of tools and unique interfaces are implemented to harness the potential of genomics in bananas, leveraging the power of comparative analysis, while recognizing the differences between datasets. Besides effective genomic tools like BLAST and the JBrowse genome browser, additional interfaces enable advanced gene search and gene family analyses including multiple alignments and phylogenies. A synteny viewer enables the comparison of genome structures between chromosome-scale assemblies. Interfaces for differential expression analyses, metabolic pathways and GO enrichment were also added. A catalogue of variants spanning the banana diversity is made available for exploration, filtering, and export to a wide variety of software. Furthermore, we implemented new ways to graphically explore gene presence-absence in pangenomes as well as genome ancestry mosaics for cultivated bananas. Besides, to guide the community in future sequencing efforts, we provide recommendations for nomenclature of locus tags and a curated list of public genomic resources (assemblies, resequencing, high density genotyping) and upcoming resources-planned, ongoing or not yet public. The Banana Genome Hub aims at supporting the banana scientific community for basic, translational, and applied research and can be accessed at https://banana-genome-hub.southgreen.fr.

Life expectancy and likelihood of surgery in multiple endocrine neoplasia type 1: AFCE and GTE cohort study.

BACKGROUND: The overall natural history, risk of death and surgical burden of patients with multiple endocrine neoplasia type 1 (MEN1) is not well known. METHODS: Patients with MEN1 from a nationwide cohort were included. The survival of patients with MEN1 was compared with that of the general population using simulated controls. The cumulative probabilities of MEN1-specific operations and postoperative mortality were assessed, and surgical sequences were analysed using sunburst charts and Venn diagrams. RESULTS: A total of 1386 patients with MEN1 were included. Life expectancy was significantly reduced in patients with MEN1 compared with simulated controls from the general population, with a lifetime difference of 15 years. Mutations affecting the JunD interaction domain had a significant negative impact on survival. Survival for patients with MEN1 compared with the general population improved over time. The probability of experiencing at least one specific MEN1 operation was above 95 per cent after 75 years, and most patients had surgery at least twice during their lifetime. Time to a 50 per cent risk of MEN1 surgery was 30.5 years for patients born after 1960, compared with 47.9 years for those born before 1960. Sex and mutations affecting the JunD interacting domain had no impact on time to first surgery. There was considerable heterogeneity in surgical sequences, with no specific clinical pathway. CONCLUSION: Life expectancy was significantly lower among patients with MEN1 compared with the general population, and further decreased in patients with mutations affecting the JunD interacting domain. Almost all patients underwent at least one MEN1-specific operation during their lifetime, but there was no standardized sequence of surgery.

GeMo: a web-based platform for the visualization and curation of genome ancestry mosaics.

In silico chromosome painting is a technique by which contributions of distinct genetic groups are represented along chromosomes of hybrid individuals. This type of analysis is used to study the mechanisms by which these individuals were formed. Such techniques are well adapted to identify genetic groups contributing to these individuals as well as hybridization events. It can also be used to follow chromosomal recombinations that occurred naturally or were generated by selective breeding. Here, we present GeMo, a novel interactive web-based and user-oriented interface to visualize in a linear-based fashion results of in silico chromosome painting. To facilitate data input generation, a script to execute analytical commands is provided and an interactive data curation mode is supported to ensure consistency of the automated procedure. GeMo contains preloaded datasets from published studies on crop domestication but can be applied to other purposes, such as breeding programs Although only applied so far on plants, GeMo can handle data from animals as well. Database URL: https://gemo.southgreen.fr/.

The immediate impact of the first waves of the global COVID-19 pandemic on agricultural systems worldwide: Reflections on the COVID-19 special issue for agricultural systems.

CONTEXT: In May 2020, approximately four months into the COVID-19 pandemic, the journal's editorial team realized there was an opportunity to collect information from a diverse range of agricultural systems on how the pandemic was playing out and affecting the functioning of agricultural systems worldwide. OBJECTIVE: The objective of the special issue was to rapidly collect information, analysis and perspectives from as many regions as possible on the initial impacts of the pandemic on global agricultural systems, The overall goal for the special issue was to develop a useful repository for this information as well as to use the journal's international reach to share this information with the agricultural systems research community and journal readership. METHODS: The editorial team put out a call for a special issue to capture the initial effects of the pandemic on the agricultural sector. We also recruited teams from eight global regions to write papers summarizing the impacts of the first waves of the pandemic in their area. RESULTS AND CONCLUSIONS: The work of the regional teams and the broader research community resulted in eight regional summary papers, as well as thirty targeted research articles. In these papers, we find that COVID-19 and global pandemic mitigation measures have had significant and sometimes unexpected impacts on our agricultural systems via shocks to agricultural labour markets, trade and value chains. And, given the high degree of overlap between low income populations and subsistence agricultural production in many regions, we also document significant shocks to food security for these populations, and the high potential for long term losses in terms of human, natural, institutional and economic capital. While we also documented instances of agricultural system resilience capacities, they were not universally accessible. We see particular need to shore up vulnerable agricultural systems and populations most negatively affected by the pandemic and to mitigate pandemic-related losses to preserve other agricultural systems policy objectives, such as improving food security, or addressing climate change. SIGNIFICANCE: Despite rapid development of vaccines, the pandemic continues to roll on as of the time of writing (early 2022). Only time will tell how the dynamics described in this Special Issue will play out in the coming years. Evidence of agricultural system resilience capacities provides some hopeful perspectives, but also highlights the need to boost these capacities across a wider cross section of agricultural systems and encourage agri-food systems transformation to prepare for more challenges ahead.

Validation of Artificial Intelligence to Support the Automatic Coding of Patient Adverse Drug Reaction Reports, Using Nationwide Pharmacovigilance Data.

INTRODUCTION: Adverse drug reaction reports are usually manually assessed by pharmacovigilance experts to detect safety signals associated with drugs. With the recent extension of reporting to patients and the emergence of mass media-related sanitary crises, adverse drug reaction reports currently frequently overwhelm pharmacovigilance networks. Artificial intelligence could help support the work of pharmacovigilance experts during such crises, by automatically coding reports, allowing them to prioritise or accelerate their manual assessment. After a previous study showing first results, we developed and compared state-of-the-art machine learning models using a larger nationwide dataset, aiming to automatically pre-code patients' adverse drug reaction reports. OBJECTIVES: We aimed to determine the best artificial intelligence model identifying adverse drug reactions and assessing seriousness in patients reports from the French national pharmacovigilance web portal. METHODS: Reports coded by 27 Pharmacovigilance Centres between March 2017 and December 2020 were selected (n = 11,633). For each report, the Portable Document Format form containing free-text information filled by the patient, and the corresponding encodings of adverse event symptoms (in Medical Dictionary for Regulatory Activities Preferred Terms) and seriousness were obtained. This encoding by experts was used as the reference to train and evaluate models, which contained input data processing and machine-learning natural language processing to learn and predict encodings. We developed and compared different approaches for data processing and classifiers. Performance was evaluated using receiver operating characteristic area under the curve (AUC), F-measure, sensitivity, specificity and positive predictive value. We used data from 26 Pharmacovigilance Centres for training and internal validation. External validation was performed using data from the remaining Pharmacovigilance Centres during the same period. RESULTS: Internal validation: for adverse drug reaction identification, Term Frequency-Inverse Document Frequency (TF-IDF) + Light Gradient Boosted Machine (LGBM) achieved an AUC of 0.97 and an F-measure of 0.80. The Cross-lingual Language Model (XLM) [transformer] obtained an AUC of 0.97 and an F-measure of 0.78. For seriousness assessment, FastText + LGBM achieved an AUC of 0.85 and an F-measure of 0.63. CamemBERT (transformer) + Light Gradient Boosted Machine obtained an AUC of 0.84 and an F-measure of 0.63. External validation for both adverse drug reaction identification and seriousness assessment tasks yielded consistent and robust results. CONCLUSIONS: Our artificial intelligence models showed promising performance to automatically code patient adverse drug reaction reports, with very similar results across approaches. Our system has been deployed by national health authorities in France since January 2021 to facilitate pharmacovigilance of COVID-19 vaccines. Further studies will be needed to validate the performance of the tool in real-life settings.

Meta-analyses frequently include old trials that are associated with a larger intervention effect: a meta-epidemiological study.

OBJECTIVE: To assess whether meta-analyses include older randomized controlled trials (RCTs) and whether intervention effect differ between older and recent RCTs. STUDY DESIGN AND SETTING: In this meta-epidemiological study of 295 meta-analyses (2940 RCTs) published in 2017-2018, we evaluated the difference in intervention effects between older (i.e., published before 2000) and recent RCTs. We also compared effects by quarters of publication year within each meta-analysis (from quarter 1 including the 25% oldest trials to quarter 4 including the 25% most recent trials). A ratio of odds ratio (ROR) <1 indicates larger effects in older than recent RCTs. RESULTS: Trials published before 2000 and before 1990 represented 25% and 10% of all trials, respectively. Intervention effects were significantly larger for old than recent RCTs (ROR = 0.92, 95% confidence interval [CI] 0.85-1.00, I2 = 22%). Compared with the most recent trials (quarter 4), intervention effects were significantly larger for the oldest trials (quarter 1) (ROR = 0.85, 95% CI 0.79-0.92) and for trials in quarter 2 (ROR = 0.89, 95% CI 0.83-0.96) but not for trials in quarter 3 (ROR = 0.98, 95% CI 0.91-1.05). CONCLUSIONS: Intervention effects were larger for older than recent RCTs. Meta-analyses including older trials should be interpreted cautiously.