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Abstract Background High‐risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by the Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline‐based therapy compared to low/intermediate‐risk patients. The biology underpinning these differential treatment outcomes remain unknown. Methods We analysed proteomic profiles and clinical outcomes of 123 eSTS patients. A Cox model for overall survival including the Sarculator was fitted to individual data to define four risk groups. A DNA replication protein signature‐Sarcoma Proteomic Module 6 (SPM6) was evaluated for association with clinicopathological factors and risk groups. SPM6 was added as a covariate together with Sarculator in a multivariable Cox model to assess improvement in prognostic risk stratification. Results DNA replication and cell cycle proteins were upregulated in high‐risk versus very low‐risk patients. Evaluation of the functional effects of CRISPR‐Cas9 gene knockdown of proteins enriched in high‐risk patients using the cancer cell line encyclopaedia database identified candidate drug targets. SPM6 was significantly associated with tumour malignancy grade (p = 1.6e‐06), histology (p = 1.4e‐05) and risk groups (p = 2.6e‐06). Cox model analysis showed that SPM6 substantially contributed to a better calibration of the Sarculator nomogram (Index of Prediction Accuracy = 0.109 for Sarculator alone versus 0.165 for Sarculator + SPM6). Conclusions Risk stratification of patient with STS is defined by distinct biological pathways across a range of cancer hallmarks. Incorporation of SPM6 protein signature improves prognostic risk stratification of the Sarculator nomogram. This study highlights the utility of integrating protein signatures for the development of next‐generation nomograms.

Abstract Objective To report on a retrospective study of primary DSRCT aiming at characterizing long‐term survivors (LTS). Methods All consecutive patients treated at our institution for a primary DSRCT between 2000 and 2021 were retrospectively identified. Patients received multiagent chemotherapy ± surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) ± whole abdomino‐pelvic radiotherapy (WAP‐RT) ± high‐dose chemotherapy ± maintenance chemotherapy (MC). Event‐free survival (EFS) and overall survival (OS) were estimated by Kaplan–Meier method. Patients alive, without evidence of disease at ≥36 months from diagnosis, were defined as LTS. Results Thirty‐eight patients were identified. All received multiagent chemotherapy; 27/38 (71%) surgery (7/27 [26%] plus HIPEC), 9/38 (24%) WAP‐RT, 12/38 (32%) MC. At a median‐follow‐up of 37 months (IQR 18–63), overall median‐EFS and median‐OS were 15 and 37 months, respectively. All events occurred within 35 months. In patients who underwent surgery, median‐EFS and median‐OS were 19 and 37 months (23 and 43 months after R0/R1, and 10 and 19 months after R2 resection), respectively. LTS were 5/38 (13%), alive at 37, 39, 53, 64, 209 months. None had liver or extra‐abdominal metastasis at diagnosis, they all received R0/R1 resection, 3/5 had WAP‐RT, 2/5 MC, 1/5 received high‐dose chemotherapy, none HIPEC. Conclusions In our series cure was likely achieved in 13% of DSRCT. LTS had no liver/extra‐abdominal disease, were treated with complete surgery, and possibly WAP‐RT/MC.

Abstract Infectious pancreatic necrosis (IPN) was assessed according to the criteria of the Animal Health Law (AHL), in particular, the criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to IPN. The assessment was performed following a methodology previously published. The outcome reported is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with an uncertain outcome. According to the assessment here performed, it is uncertain whether IPN can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (50–90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that IPN does not meet the criteria in Section 1 (Category A; 0–1% probability of meeting the criteria) and it is uncertain whether it meets the criteria in Sections 2, 3, 4 and 5 (Categories B, C, D and E; 33–66%, 33–66%, 50–90% and 50–99% probability of meeting the criteria, respectively). The animal species to be listed for IPN according to Article 8 criteria are provided.

Abstract This Scientific Opinion addresses a European Commission request on the welfare of calves as part of the Farm to Fork strategy. EFSA was asked to provide a description of common husbandry systems and related welfare consequences, as well as measures to prevent or mitigate the hazards leading to them. In addition, recommendations on three specific issues were requested: welfare of calves reared for white veal (space, group housing, requirements of iron and fibre); risk of limited cow–calf contact; and animal‐based measures (ABMs) to monitor on‐farm welfare in slaughterhouses. The methodology developed by EFSA to address similar requests was followed. Fifteen highly relevant welfare consequences were identified, with respiratory disorders, inability to perform exploratory or foraging behaviour, gastroenteric disorders and group stress being the most frequent across husbandry systems. Recommendations to improve the welfare of calves include increasing space allowance, keeping calves in stable groups from an early age, ensuring good colostrum management and increasing the amounts of milk fed to dairy calves. In addition, calves should be provided with deformable lying surfaces, water via an open surface and long‐cut roughage in racks. Regarding specific recommendations for veal systems, calves should be kept in small groups (2–7 animals) within the first week of life, provided with ~ 20 m2/calf and fed on average 1 kg neutral detergent fibre (NDF) per day, preferably using long‐cut hay. Recommendations on cow–calf contact include keeping the calf with the dam for a minimum of 1 day post‐partum. Longer contact should progressively be implemented, but research is needed to guide this implementation in practice. The ABMs body condition, carcass condemnations, abomasal lesions, lung lesions, carcass colour and bursa swelling may be collected in slaughterhouses to monitor on‐farm welfare but should be complemented with behavioural ABMs collected on farm.

Abstract This scientific opinion focuses on the welfare of laying hens, pullets and layer breeders on farm. The most relevant husbandry systems used in Europe are described. For each system, highly relevant welfare consequences were identified, as well as related animal‐based measures (ABMs), and hazards leading to the welfare consequences. Moreover, measures to prevent or correct the hazards and/or mitigate the welfare consequences are recommended. The highly relevant welfare consequences based on severity, duration and frequency of occurrence are bone lesions, group stress, inability to avoid unwanted sexual behaviour, inability to perform comfort behaviour, inability to perform exploratory or foraging behaviour, isolation stress, predation stress, resting problems, restriction of movement, skin disorders and soft tissue lesions and integument damage. The welfare consequences of non‐cage compared to cage systems for laying hens are described and minimum enclosure characteristics are described for laying hens, pullets and layer breeders. Beak trimming, which causes negative welfare consequences and is conducted to reduce the prevalence and severity of pecking, is described as well as the risks associated with rearing of non‐beak‐trimmed flocks. Alternatives to reduce sharpness of the beak without trimming are suggested. Finally, total mortality, plumage damage, wounds, keel bone fractures and carcass condemnations are the most promising ABMs for collection at slaughterhouses to monitor the level of laying hen welfare on farm. Main recommendations include housing all birds in non‐cage systems with easily accessible, elevated platforms and provision of dry and friable litter and access to a covered veranda. It is further recommended to implement protocols to define welfare trait information to encourage progress in genetic selection, implement measures to prevent injurious pecking, rear pullets with dark brooders and reduce male aggression in layer breeders.

Abstract This Scientific Opinion considers the welfare of domestic fowl (Gallus gallus) related to the production of meat (broilers) and includes the keeping of day‐old chicks, broiler breeders, and broiler chickens. Currently used husbandry systems in the EU are described. Overall, 19 highly relevant welfare consequences (WCs) were identified based on severity, duration and frequency of occurrence: ‘bone lesions’, ‘cold stress’, ‘gastro‐enteric disorders’, ‘group stress’, ‘handling stress’, ‘heat stress’, ‘isolation stress’, ‘inability to perform comfort behaviour’, ‘inability to perform exploratory or foraging behaviour’, ‘inability to avoid unwanted sexual behaviour’, ‘locomotory disorders’, ‘prolonged hunger’, ‘prolonged thirst’, ‘predation stress’, ‘restriction of movement’, ‘resting problems’, ‘sensory under‐ and overstimulation’, ‘soft tissue and integument damage’ and ‘umbilical disorders’. These WCs and their animal‐based measures (ABMs) that can identify them are described in detail. A variety of hazards related to the different husbandry systems were identified as well as ABMs for assessing the different WCs. Measures to prevent or correct the hazards and/or mitigate each of the WCs are listed. Recommendations are provided on quantitative or qualitative criteria to answer specific questions on the welfare of broilers and related to genetic selection, temperature, feed and water restriction, use of cages, light, air quality and mutilations in breeders such as beak trimming, de‐toeing and comb dubbing. In addition, minimal requirements (e.g. stocking density, group size, nests, provision of litter, perches and platforms, drinkers and feeders, of covered veranda and outdoor range) for an enclosure for keeping broiler chickens (fast‐growing, slower‐growing and broiler breeders) are recommended. Finally, ‘total mortality’, ‘wounds’, ‘carcass condemnation’ and ‘footpad dermatitis’ are proposed as indicators for monitoring at slaughter the welfare of broilers on‐farm.

Abstract The epidemiological situation of SARS‐CoV‐2 in humans and animals is continually evolving. To date, animal species known to transmit SARS‐CoV‐2 are American mink, raccoon dog, cat, ferret, hamster, house mouse, Egyptian fruit bat, deer mouse and white‐tailed deer. Among farmed animals, American mink have the highest likelihood to become infected from humans or animals and further transmit SARS‐CoV‐2. In the EU, 44 outbreaks were reported in 2021 in mink farms in seven MSs, while only six in 2022 in two MSs, thus representing a decreasing trend. The introduction of SARS‐CoV‐2 into mink farms is usually via infected humans; this can be controlled by systematically testing people entering farms and adequate biosecurity. The current most appropriate monitoring approach for mink is the outbreak confirmation based on suspicion, testing dead or clinically sick animals in case of increased mortality or positive farm personnel and the genomic surveillance of virus variants. The genomic analysis of SARS‐CoV‐2 showed mink‐specific clusters with a potential to spill back into the human population. Among companion animals, cats, ferrets and hamsters are those at highest risk of SARS‐CoV‐2 infection, which most likely originates from an infected human, and which has no or very low impact on virus circulation in the human population. Among wild animals (including zoo animals), mostly carnivores, great apes and white‐tailed deer have been reported to be naturally infected by SARS‐CoV‐2. In the EU, no cases of infected wildlife have been reported so far. Proper disposal of human waste is advised to reduce the risks of spill‐over of SARS‐CoV‐2 to wildlife. Furthermore, contact with wildlife, especially if sick or dead, should be minimised. No specific monitoring for wildlife is recommended apart from testing hunter‐harvested animals with clinical signs or found‐dead. Bats should be monitored as a natural host of many coronaviruses.

Abstract In the framework of its Farm to Fork Strategy, the Commission is undertaking a comprehensive evaluation of animal welfare legislation. This opinion deals with the protection of horses and donkeys during transport. While the opinion focuses primarily on road transport of horses, there are specific sections dealing with the transport of horses on roll‐on–roll‐off ferries, horses transported by air and the transport of donkeys. In addition, the opinion covers welfare concerns in relation to a specific scenario identified by the European Commission related to the transport of horses on long journeys to slaughterhouses. Current practices related to transport of horses during the different stages (preparation, loading and unloading, transit and the journey breaks) are described. Overall, 13 welfare consequences were identified as being highly relevant for the welfare of horses during transport based on severity, duration and frequency of occurrence: gastro‐enteric disorders, handling stress, heat stress, injuries, isolation stress, motion stress, prolonged hunger, prolonged thirst, respiratory disorders, resting problems, restriction of movement, sensory overstimulation and separation stress. These welfare consequences and their animal‐based measures are described. A variety of hazards were identified related to factors such as inexperienced/untrained handlers, lack of horse training, structural deficiencies of vehicles/facilities, poor driving skills/conditions, horse separation/regrouping, unfavourable microclimatic and environmental conditions and poor husbandry practices. The opinion contains general and specific conclusions in relation to the different stages of transport. Recommendations to prevent hazards and correct or mitigate welfare consequences have been developed. Recommendations were also developed to define quantitative thresholds for microclimatic conditions within the means of transport and for space allowance. The development of welfare consequences over time was assessed in relation to maximum journey time.

Abstract In the framework of its Farm to Fork Strategy, the Commission is undertaking a comprehensive evaluation of the animal welfare legislation. The present Opinion deals with protection of cattle (including calves) during transport. Welfare of cattle during transport by road is the main focus, but other means of transport are also covered. Current practices related to transport of cattle during the different stages (preparation, loading/unloading, transit and journey breaks) are described. Overall, 11 welfare consequences were identified as being highly relevant for the welfare of cattle during transport based on severity, duration and frequency of occurrence: group stress, handling stress, heat stress, injuries, motion stress, prolonged hunger, prolonged thirst, respiratory disorders, restriction of movement, resting problems and sensory overstimulation. These welfare consequences and their animal‐based measures are described. A variety of hazards, mainly relating to inexperienced/untrained handlers, inappropriate handling, structural deficiencies of vehicles and facilities, poor driving conditions, unfavourable microclimatic and environmental conditions, and poor husbandry practices leading to these welfare consequences were identified. The Opinion contains general and specific conclusions relating to the different stages of transport for cattle. Recommendations to prevent hazards and to correct or mitigate welfare consequences have been developed. Recommendations were also developed to define quantitative thresholds for microclimatic conditions within the means of transport and spatial thresholds (minimum space allowance). The development of welfare consequences over time was assessed in relation to maximum journey duration. The Opinion covers specific animal transport scenarios identified by the European Commission relating to transport of unweaned calves, cull cows, the export of cattle by livestock vessels, the export of cattle by road, roll‐on‐roll‐off ferries and ‘special health status animals’, and lists welfare concerns associated with these.

Abstract In the framework of its Farm to Fork Strategy, the Commission is undertaking a comprehensive evaluation of the animal welfare legislation. The present Opinion deals with protection of pigs during transport. The welfare of pigs during transport by road is the main focus, but other means of transport are also covered. Current practices related to transport of pigs during the different stages (preparation, loading/unloading, transit and journey breaks) are described. Overall, 10 welfare consequences were identified as highly relevant for the welfare of pigs during transport based on the severity, duration and frequency of occurrence: group stress, handling stress, heat stress, injuries, motion stress, prolonged hunger, prolonged thirst, restriction of movement, resting problems and sensory overstimulation. These welfare consequences and their animal‐based measures are described. A variety of hazards were identified, mainly relating to factors such as mixing of unfamiliar pigs, inappropriate handling methods and devices, the use of pick‐up pens, inexperienced/untrained handlers, structural deficiencies of vehicles and facilities, poor driving conditions, unfavourable microclimatic and environmental conditions and poor husbandry practices leading to these welfare consequences. The Opinion contains general and specific conclusions relating to the different stages of transport of pigs. Recommendations to prevent hazards and to correct or mitigate welfare consequences are made. Recommendations were also developed to define quantitative thresholds for microclimatic conditions and minimum space allowance within means of transport. The development of the welfare consequences over time was assessed in relation to maximum journey duration. The Opinion covers specific animal transport scenarios identified by the European Commission relating to transport of cull sows and ‘special health status animals’, and lists welfare concerns associated with these.

Abstract In the framework of its Farm to Fork Strategy, the Commission is undertaking a comprehensive evaluation of animal welfare legislation. The present Opinion deals with the protection of small ruminants (sheep and goats) during transport. The main focus is on welfare of sheep during transport by road but other means of transport and concerns for welfare of goats during transport are also covered. Current practices related to transport of sheep during the different stages (preparation, loading and unloading, transit and journey breaks) are described. Overall, 11 welfare consequences were identified as being highly relevant for the welfare of sheep during transport based on severity, duration and frequency of occurrence: group stress, handling stress, heat stress, injuries, motion stress, predation stress, prolonged hunger, prolonged thirst, restriction of movement, resting problems and sensory overstimulation. These welfare consequences and their animal‐based measures are described. A wide variety of hazards, mainly relating to inappropriate or aggressive handling of animals, structural deficiencies of vehicles and facilities, unfavourable microclimatic and environmental conditions and poor husbandry practices, leading to these welfare consequences were identified. The Opinion contains general and specific conclusions in relation to the different stages of transport. Recommendations to prevent hazards and to correct or mitigate welfare consequences have been developed. Recommendations were also developed to define quantitative thresholds for microclimatic conditions within the means of transport and spatial thresholds (minimum space allowance). The development of welfare consequences over time were assessed in relation to maximum journey time. The Opinion covers specific animal transport scenarios identified by the European Commission relating to the export of sheep by livestock vessels, export of sheep by road, roll‐on‐roll‐off vessels and ‘special health status animals’, and lists welfare concerns associated with these.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of prohibitions of certain activities in restricted zones, and of certain risk mitigation treatments for products of animal origin and other materials with respect to diseases included in the Category A list in the Animal Health Law (Regulation (EU) 2016/429). This opinion belongs to a series of opinions where other disease‐specific control measures have been assessed. In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of (i) prohibiting the movements of certain products, notably germinal products (semen, oocytes, embryos and hatching eggs), products of animal origin and animal by‐products and feed of plant origin, hay and straw, and (ii) risk mitigation treatments for products of animal origin. In terms of semen, oocytes, embryos and hatching eggs, it was agreed that there was a lack of evidence particularly for embryos and oocytes reflected in a varying degree of uncertainty, whether these commodities could potentially contain the pathogen under consideration. The scenario assessed did not consider whether the presence of pathogen would lead to infection in the recipient animal. In terms of animal products, certain animal by‐products and movement of feed of plant origin and straw, the assessment considered the ability of the commodity to transmit disease to another animal if exposed. For most pathogens, products were to some degree considered a risk, but lack of field evidence contributed to the uncertainty, particularly as potential exposure of ruminants to meat products is concerned. In terms of the risk mitigating treatments, recommendations have been made for several of these treatments, because the treatment description is not complete, the evidence is poor or inconclusive, or the evidence points to the treatment being ineffective.

Abstract This document provides methodological guidance developed by the EFSA Panel on Animal Health and Welfare to produce Scientific Opinions in response to mandates received from the European Commission in the context of the Farm to Fork Strategy. The mandates relate to the welfare of (i) animals during transport, (ii) calves, (iii) laying hens, (iv) broilers, (v) pigs, (vi) ducks, geese and quails, and (vii) dairy cows. This guidance was developed in order to define the methods and strategy to be applied for responding to the Terms of Reference (ToRs) of the mandates. The mandates each consist of a set of General ToRs which refer to the husbandry systems used in the production of each animal species or the current transport practices for free moving animals and animals transported in cages, and a set of specific ToRs for which difficulties in ensuring animal welfare have been identified and where specific scenarios are envisaged. Part I of the guidance includes a description of welfare consequences for the animals. Part II includes a new methodology for providing quantitative recommendations regarding animal welfare. The proposed methodology follows the assumption that the effect of an exposure variable (e.g. space allowance) on animal welfare can be quantified by comparing the expression of an animal‐based measure (ABM) under ‘unexposed conditions’ (e.g. unlimited space) and under high exposure (e.g. restrictive conditions). The level of welfare as assessed through this ABM can be quantified for different levels of the exposure variable (e.g. at increasing space allowances) and quantitative recommendations can thus be provided. The final version of the methodological guidance was endorsed for public consultation, which took place between 14 February 2022 and 31 March 2022. The comments received are integrated in this document.

Abstract Escherichia coli (E. coli) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for dogs and cats, horses, swine, poultry, cattle, sheep and goats in previous scientific opinions. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR E. coli can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2, 3 and 4 (Categories A, B, C and D; 0–5%, 5–10%, 10–33% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel was uncertain whether it meets the criteria in Section 5 (Category E, 33–66% probability of meeting the criteria). The animal species to be listed for AMR E. coli according to Article 8 criteria include mammals, birds, reptiles and fish.

Abstract Staphylococcus aureus (S. aureus) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for cattle and horses in previous scientific opinions. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR S. aureus can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (60–90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 4 (Categories A, B and D; 1–5%, 5–10% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel was uncertain whether it meets the criteria in Sections 3 and 5 (Categories C and E, 33–90% and 60–90% probability of meeting the criteria, respectively). The animal species to be listed for AMR S. aureus according to Article 8 criteria include mainly mammals, birds, reptiles and fish.

Abstract Pseudomonas aeruginosa (P. aeruginosa) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for dogs and cats in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR P. aeruginosa can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2, 3 and 4 (Categories A, B, C and D; 0–5%, 1–5%, 5–33% and 5–33% probability of meeting the criteria, respectively) and the AHAW Panel was uncertain whether it meets the criteria in Section 5 (Category E, 33–90% probability of meeting the criteria). The animal species to be listed for AMR P. aeruginosa according to Article 8 criteria are mainly dogs and cats.

Abstract The EFSA asked the Panel on Animal Health and Welfare to develop a guidance document on good practice in conducting scientific assessments in animal health using modelling. In previous opinions, the AHAW Panel has responded to two‐thirds of animal health‐related mandates using some kind of modelling. These models range from simple to complex, employing a combination of scientific, economic, socio‐economic or other types of data. Hence, there is strong interest in the development of a guidance document to integrate modelling efforts into the routine process of EFSA working groups. In this document, an ‘operating procedure' (OP) for the use of modelling within an AH working group is presented. The OP provides a detailed flowchart enabling modelling to be transparently and consistently integrated in the assessment. The OP is structured into phases. These phases combine the relevant standard operating procedures and working instructions of EFSA with the modelling process. Each phase includes roles and actions to be taken, expected output and the sequence of agreements that need to be made between all partners in the scientific assessment. In conclusion, it is expected that adherence to the OP will improve transparency of models in EFSA outputs, and it is recommended to adopt it as a standard procedure when responding to AHAW mandates.

As more adults survive with congenital heart disease, the need to better understand the long‐term complications, and comorbid disease will become increasingly important. Improved care and survival into the early and late adult years for all patients equitably requires accurate, timely, and comprehensive data to support research and quality‐based initiatives. National data collection in adult congenital heart disease will require a sound foundation emphasizing core ethical principles that acknowledge patient and clinician perspectives and promote national collaboration. In this document we examine these foundational principles and offer suggestions for developing an ethically responsible and inclusive framework for national ACHD data collection.

Despite the overall improvement in life expectancy of patients living with congenital heart disease (congenital HD), disparities in morbidity and mortality remain throughout the lifespan. Longstanding systemic inequities, disparities in the social determinants of health, and the inability to obtain quality lifelong care contribute to poorer outcomes. To work toward health equity in populations with congenital HD, we must recognize the existence and strategize the elimination of inequities in overall congenital HD morbidity and mortality, disparate health care access, and overall quality of health services in the context of varying social determinants of health, systemic inequities, and structural racism. This requires critically examining multilevel contributions that continue to facilitate health inequities in the natural history and consequences of congenital HD. In this scientific statement, we focus on population, systemic, institutional, and individual‐level contributions to health inequities from prenatal to adult congenital HD care. We review opportunities and strategies for improvement in lifelong congenital HD care based on current public health and scientific evidence, surgical data, experiences from other patient populations, and recognition of implicit bias and microaggressions. Furthermore, we review directions and goals for both quantitative and qualitative research approaches to understanding and mitigating health inequities in congenital HD care. Finally, we assess ways to improve the diversity of the congenital HD workforce as well as ethical guidance on addressing social determinants of health in the context of clinical care and research.

Abstract Brachyspira hyodysenteriae (B. hyodysenteriae) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for swine in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR B. hyodysenteriae can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 3 (Categories A, B and C; 1–10%, 10–33% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel was uncertain whether it meets the criteria in Sections 4 and 5 (Categories D and E, 50–90% and 33–66% probability of meeting the criteria, respectively). The main animal species to be listed for AMR B. hyodysenteriae according to Article 8 criteria are pigs and some species of birds, such as chickens and ducks.

Abstract Background Sunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment. Methods Patients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow‐mediated dilation (FMD), carotid intima media thickness (IMT), ankle‐brachial pressure index (ABI), and 24‐hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1. Results Twenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P

Abstract Aims Ventilation vs. carbon dioxide production (VE/VCO2) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. Methods and results We calculated the linear regressions between age and VE/VCO2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13–83 years). We then applied age‐adjusted and sex‐adjusted formulas to predict VE/VCO2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO2 14.8 ± 4.9, mL/min/kg, VE/VCO2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO2 < 14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO2 = 0.052 × Age + 23.808 (r = 0.192); male, VE/VCO2 = 0.095 × Age + 20.227 (r = 0.371) (P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO2 values. The 2‐year survival prognostic power of VE/VCO2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO2 < 14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015). Conclusions The percentage of predicted VE/VCO2 slope value strengthens the prognostic power of VE/VCO2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.

Abstract Staphylococcus pseudintermedius (S. pseudintermedius) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for dogs and cats in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR S. pseudintermedius can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (30–90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 4 (Categories A, B and D; 0–1%, 1–10% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel is uncertain whether it meets the criteria in Sections 3 and 5 (Categories C and E, 5–66% and 30–90% probability of meeting the criteria, respectively). The animal species to be listed for AMR S. pseudintermedius according to Article 8 criteria are mostly species belonging to the families of Canidae and Felidae, such as dogs and cats.

Abstract In this Opinion, the antimicrobial‐resistant bacteria responsible for transmissible diseases that constitute a threat to the health of certain kept fish species have been assessed. Atlantic salmon (Salmo salar), carp (Cyprinus spp.), rainbow trout (Oncorhynchus mykiss), sea bream (Sparus aurata) and tilapia (Oreochromis spp.), selected as representative of the most important fish species and production systems that are commercially reared in fresh and saltwater farms, were the focus of this assessment. The assessment was performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate Opinion. The global state of play of antimicrobial resistance in Aeromonas hydrophila, Aeromonas salmonicida, Flavobacterium psychrophilum and Flavobacterium columnare is provided. Among these bacteria, none was identified as being among the most relevant antimicrobial‐resistant bacteria in the assessed kept fish species in the EU due to the very limited scientific evidence available.

Abstract Rhodococcus equi (R. equi) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for horses in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR R. equi can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (10–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1 and 2 (Categories A and B; 5–10% and 10–33% probability of meeting the criteria, respectively), and the AHAW Panel is uncertain whether it meets the criteria in Sections 3, 4 and 5 (Categories C, D and E; 10–66% probability of meeting the criteria in all three categories). The animal species to be listed for AMR R. equi according to Article 8 criteria are mainly horses and other species belonging to the Perissodactyla and Artiodactyla orders.

Abstract Enterococcus faecalis (E. faecalis) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for poultry in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR E. faecalis can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 4 (Categories A, B and D; 0–5%, 5–10% and 1–10% probability of meeting the criteria, respectively) and the AHAW Panel is uncertain whether it meets the criteria in Sections 3 and 5 (Categories C and E, 33–66% and 33–66% probability of meeting the criteria, respectively). The animal species to be listed for AMR E. faecalis according to Article 8 criteria are mostly birds of the orders Galliformes and Anseriformes, but also mammals and reptiles can serve as reservoirs.

Abstract Enterococcus cecorum (E. cecorum) was identified among the most relevant antimicrobial‐resistant (AMR) bacteria in the EU for poultry in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR E. cecorum can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–75% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 4 (Categories A, B and D; 0–5%, 5–10% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel is uncertain whether it meets the criteria in Sections 3 and 5 (Categories C and E, 33–66% and 33–75% probability of meeting the criteria, respectively). The animal species to be listed for AMR E. cecorum according to Article 8 criteria are mostly birds belonging to the families of Anatidae, Columbidae and Phasianidae.

Abstract EFSA received a mandate from the EC to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases (‘Animal Health Law’). This opinion belongs to a series of opinions where these control measures are assessed, with this opinion covering the assessment of control measures for Lumpy Skin Disease (LSD). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: i) clinical and laboratory sampling procedures, ii) monitoring period and iii) the minimum radius of the protection and surveillance zones, and the minimum length of time that measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere; nonetheless, the transmission kernels used for the assessment of the minimum radius of the protection and surveillance zones are shown. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. The monitoring period was assessed as effective, and based on the transmission kernels available, it was concluded that the protection zone of 20 km radius and the surveillance zone of 50 km radius would comprise > 99% of the transmission from an affected establishment if transmission occurred. Recommendations provided for each of the assessed scenarios aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to LSD.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases ('Animal Health Law’). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for glanders. In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radius of the protection and surveillance zone, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere. Considering the epidemiology and distribution of glanders, it was foreseen that three different situations could lead to a suspicion of the disease. Sampling procedures were defined for each of the three different suspicion types, which can also be applied in most of the other scenarios assessed. The monitoring period (6 months) was assessed as effective in all scenarios. The AHAW Panel of experts considered the minimum radius and duration of the existing protection and surveillance zone, set at the establishment level, effective. Recommendations provided for each of the scenarios assessed aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to glanders.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases (‘Animal Health Law’). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for Contagious Bovine Pleuropneumonia (CBPP). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period, (iii) the minimum radius of the protection and surveillance zones, and (iv) the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. Different clinical and laboratory sampling procedures are proposed depending on the scenarios considered. The monitoring period of 45 days was assessed as not effective and at least 90 days (3 months) is recommended in affected areas where high awareness is expected; when the index case occurs in an area where the awareness is low the monitoring period should be at least 180 days (6 months). Since transmission kernels do not exist and data to estimate transmission kernels are not available, the effectiveness of surveillance and protection zones for CBPP was based on expert knowledge. A surveillance zone of 3 km was considered effective, while a protection zone including establishments adjacent to affected ones is recommended. Recommendations, provided for each of the scenarios assessed, aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to CBPP.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases ('Animal Health Law’). This opinion belongs to a series of opinions where these control measures were assessed for several diseases, with this opinion covering the assessment of control measures for Rift Valley Fever (RVF). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radius of the protection and surveillance zone and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere; nonetheless, the transmission kernels used for the assessment of the minimum radius of the protection and surveillance zones are shown. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. Different risk‐based sampling procedures based on clinical visits and laboratory testing are assessed in case of outbreak suspicion, granting animal movements and for repopulation purposes. The length of monitoring period and minimum duration of measures to be implemented in the restricted zones as defined in the Delegated Regulation (30 days) are considered effective for the investigation and control of suspected and confirmed RVF outbreaks, as well as the size of protection and surveillance zone of 20 and 50 km, respectively, which are assessed as sufficient to contain disease transmission with at least 95% probability.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases ('Animal Health Law’). This opinion belongs to a series of opinions where these control measures are assessed, with this opinion covering the assessment of control measures for rinderpest (RP), the only animal disease to have been globally eradicated. In this opinion, the AHAW Panel reviewed the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radius of the protection and surveillance zone, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere. The transmission kernels used for the assessment of the minimum radius of the protection and surveillance zones are shown. Several scenarios for which control measures had to be assessed were agreed prior to the assessment. Considering that RP has been eradicated globally, a re‐emergence that is not stopped in its early phases could have a devastating impact on animal health and the economy. The panel concludes that no suitable strategies are available to entirely mitigate the risk associated with granting derogations from killing of animals in an affected establishment or for animal movements. Therefore, the panel recommends to not grant any derogations. The monitoring period of 21 days was assessed as effective, except for the hypothetical first re‐emergence of RP, when lack of awareness and diagnostic capability may extend the time to detection. It was concluded that the protection and the surveillance zones would contain 90% and > 99%, respectively, of the infections from an affected establishment. Enlarging the protection zone to 4 km would contain the disease spread with 95% probability.

Abstract Equine Herpesvirus‐1 infection has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of: Article 7 on disease profile and impacts, Article 5 on the eligibility of the disease to be listed, Article 9 for the categorisation of the disease according to disease prevention and control measures as in Annex IV and Article 8 on the list of animal species related to Equine Herpesvirus‐1 infection. The assessment has been performed following a methodology composed of information collection and compilation, and expert judgement on each criterion at individual and collective level. The outcome is the median of the probability ranges provided by the experts, which indicates whether the criterion is fulfilled (66–100%) or not (0–33%), or whether there is uncertainty about fulfilment (33–66%). For the questions where no consensus was reached, the different supporting views are reported. According to the assessment performed, Equine Herpesvirus‐1 infection can be considered eligible to be listed for Union intervention according to Article 5 of the Animal Health Law with 33–90% certainty. According to the criteria as in Annex IV of the AHL related to Article 9 of the AHL for the categorisation of diseases according to the level of prevention and control, it was assessed with less than 1% certainty that EHV‐1 fulfils the criteria as in Section 1 (category A), 1–5% for the criteria as in Section 2 (category B), 10–66% for the criteria as in Section 3 (category C), 66–90% for the criteria as in Section 4 (category D) and 33–90% for the criteria as in Section 5 (category E). The animal species to be listed for EHV‐1 infection according to Article 8(3) criteria are the species belonging to the families of Equidae, Bovidae, Camelidae, Caviidae, Cervidae, Cricetidae, Felidae, Giraffidae, Leporidae, Muridae, Rhinocerontidae, Tapiridae and Ursidae.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases (‘Animal Health Law’). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for Contagious Caprine Pleuropneumonia (CCPP). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period, (iii) the minimum radius of the protection and surveillance zones and iv) the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. Different clinical and laboratory sampling procedures are proposed depending on the scenarios considered. The monitoring period of 45 days was assessed as effective in affected areas where high awareness is expected, and when the index case occurs in an area where the awareness is low the monitoring period should be at least 180 days (6 months). Since transmission kernels do not exist and data to estimate transmission kernels are not available, a surveillance zone of 3 km was considered effective based on expert knowledge, while a protection zone should also be developed to include establishments adjacent to affected ones. Recommendations, provided for each of the scenarios assessed, aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to CCPP.

Abstract Aims Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF. Methods and results Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline‐based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M‐mode, two‐dimensional, and Doppler echocardiographic examination, and an incremental symptom‐limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One‐year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT‐proBNP levels (−35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow‐up period. Conclusions Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.

Abstract In this opinion, the antimicrobial‐resistant bacteria responsible for transmissible diseases that constitute a threat to the health of pigs have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play of antimicrobial resistant Escherichia coli, Streptococcus suis, Actinobacillus pleuropneumoniae, Pasteurella multocida, Glaeserella parasuis, Bordetella bronchiseptica, Staphylococcus aureus, Staphylococcus hyicus, Brachyspira hyodysenteriae, Trueperella pyogenes, Erysipelothrix rhusiopathiae, Streptococcus dysgalactiae, Mycoplasma hyosynoviae, Mycoplasma hyorhinis, Mycoplasma hyopneumoniae and Brachyspira pilosicoli has been provided. Among those bacteria, EFSA identified E. coli and B. hyodysenteriae with > 66% certainty as being the most relevant antimicrobial resistant bacteria in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases (‘Animal Health Law’). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for sheep and goat pox. In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radii of the protection and surveillance zones, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere; nonetheless, the transmission kernels used for the assessment of the minimum radii of the protection and surveillance zones are shown. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. Different risk‐based sampling procedures based on clinical visits and laboratory testing are assessed in case of outbreak suspicion, granting animal movements and for repopulation purposes. The monitoring period of 21 days was assessed as effective. The estimated probability of transmission beyond the protection zone of 3 km radius from an infectious establishment is 9.6% (95% CI: 3.1–25.8%) and 2.3% (95% CI: 1–5.5%) for the surveillance zone of 10 km radius. This may be considered sufficient to contain the disease spread (95% probability of containing transmission corresponds to 5.3 Km). To contain 99% of the spread, the radius should be increased to 19.4 km (95% CI: 9.8–26.8). This may increase the number of farms in the surveillance zone, since the area would increase fourfold.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases (‘Animal Health Law’). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for Newcastle disease (ND). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radius of the protection and surveillance zone, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. The monitoring period (21 days) was assessed as effective in non‐vaccinated chicken and turkey flocks, although large uncertainty remains surrounding the effectiveness of this period in vaccinated galliform flocks and flocks of other bird species. It was also concluded that the protection (3 km radius) and the surveillance (10 km radius) zones contain 99% of the infections from an infectious establishment. Recommendations provided for each of the scenarios assessed aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to ND.

Abstract In this opinion, the antimicrobial‐resistant bacteria responsible for transmissible diseases that constitute a threat to poultry health have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play is provided for: Avibacterium (Haemophilus) paragallinarum, Bordetella avium, Clostridium perfringens, Enterococcus faecalis and Enterococcus cecorum, Erysipelothrix rhusiopathiae, Escherichia coli, Gallibacterium spp., Mycoplasma synoviae, Ornithobacterium rhinotracheale, Pasteurella multocida, Riemerella anatipestifer and Staphylococcus aureus. Among those bacteria, EFSA identified Escherichia coli, Enterococcus faecalis and Enterococcus cecorum with ≥ 66% certainty as being the most relevant antimicrobial resistant bacteria in the EU based on the available evidence. The animal health impact of these most relevant bacteria, and their eligibility for being listed and categorised within the Animal Health Law Framework, will be assessed in separate scientific opinions.

Abstract In this opinion, the antimicrobial‐resistant bacteria responsible for transmissible diseases that constitute a threat to the health of farmed rabbits have been assessed. The assessment has been performed following a methodology based on information collected through an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play on antimicrobial resistance in clinical isolates of Pasteurella multocida, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bordetella bronchiseptica, Clostridium difficile, Clostridium perfringens and Clostridium spiroforme is provided. Among these bacteria, none were identified as being the most relevant antimicrobial‐resistant bacteria in rabbits in the EU due to the very limited scientific evidence available.

Abstract In this opinion, the antimicrobial resistant bacteria responsible for transmissible diseases that constitute a threat to the health of cattle have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play on antimicrobial resistance in clinical isolates of Escherichia coli (non‐VTEC), Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus uberis, Streptococcus dysgalactiae, Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Moraxella bovis, Fusobacterium necrophorum and Trueperella pyogenes is provided. Among those bacteria, EFSA identified E. coli and S. aureus with ≥ 66% certainty as being the most relevant antimicrobial resistant bacteria in cattle in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Abstract In this opinion, the antimicrobial‐resistant bacteria responsible for transmissible diseases that constitute a threat to the health of horses have been assessed. The assessment has been performed following a methodology composed of information collected via an extensive literature review and expert judgement. Details on the methodology used for this assessment are explained in a separate opinion. A global state of play of antimicrobial‐resistant Actinobacillus equuli, Dermatophilus congolensis, Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, Pasteurella spp., Pseudomonas aeruginosa, Rhodococcus equi, Staphylococcus aureus and Streptococcus dysgalactiae subsp. dysgalactiae/equisimilis and Streptococcus equi subsp. equi and subsp. zooepidemicus has been provided. Among those bacteria, EFSA identified E. coli, Staphylococcus aureus and R. equi with more than 66% certainty as the most relevant antimicrobial‐resistant bacteria in the EU, given their importance as causative agents of clinical disease in horses and the significant levels of resistance to clinically relevant antimicrobials. The animal health impact of these ‘most relevant’ bacteria as well as their eligibility of being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Abstract The killing of sheep and goats for human consumption (slaughtering) can take place in a slaughterhouse or on‐farm. The processes of slaughtering that were assessed for welfare, from the arrival of sheep and goats until their death (including slaughtering without stunning), were grouped into three main phases: pre‐stunning (including arrival, unloading from the truck, lairage, handling and moving of sheep and goats); stunning (including restraint); and bleeding. Stunning methods were grouped into two categories: mechanical and electrical. Twelve welfare consequences that sheep and goats may experience during slaughter were identified: heat stress, cold stress, fatigue, prolonged thirst, prolonged hunger, impeded movement, restriction of movements, resting problems, social stress, pain, fear and distress. These welfare consequences and their relevant animal‐based measures are described in detail in this Scientific Opinion. In total, 40 welfare hazards that could occur during slaughter were identified and characterised, most of them related to stunning and bleeding. Staff were identified as the origin of 39 hazards, which were attributed to the lack of appropriate skill sets needed to perform tasks or to fatigue. Measures to prevent and correct hazards were identified, and structural and managerial measures were identified as those with a crucial role in prevention. Outcome tables linking hazards, welfare consequences, animal‐based measures, origin of hazards and preventive and corrective measures were developed for each process. Mitigation measures to minimise welfare consequences are proposed.

Background Congenital heart disease practices and outcomes vary significantly across centers, including postoperative chest tube (CT) management, which may impact postoperative length of stay (LOS). We used collaborative learning methods to determine whether centers could adapt and safely implement best practices for CT management, resulting in reduced postoperative CT duration and LOS. Methods and Results Nine pediatric heart centers partnered together through 2 learning networks. Patients undergoing 1 of 9 benchmark congenital heart operations were included. Baseline data were collected from June 2017 to June 2018, and intervention‐phase data were collected from July 2018 to December 2019. Collaborative learning methods included review of best practices from a model center, regular data feedback, and quality improvement coaching. Center teams adapted CT removal practices (eg, timing, volume criteria) from the model center to their local resources, practices, and setting. Postoperative CT duration in hours and LOS in days were analyzed using statistical process control methodology. Overall, 2309 patients were included. Patient characteristics did not differ between the study and intervention phases. Statistical process control analysis showed an aggregate 15.6% decrease in geometric mean CT duration (72.6 hours at baseline to 61.3 hours during intervention) and a 9.8% reduction in geometric mean LOS (9.2 days at baseline to 8.3 days during intervention). Adverse events did not increase when comparing the baseline and intervention phases: CT replacement (1.8% versus 2.0%, P=0.56) and readmission for pleural effusion (0.4% versus 0.5%, P=0.29). Conclusions We successfully lowered postoperative CT duration and observed an associated reduction in LOS across 9 centers using collaborative learning methodology.

Abstract EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases (‘Animal Health Law’). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for Classical swine fever (CSF). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radii of the protection and surveillance zones, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere; nonetheless, details of the model used for answering these questions are presented in this opinion as well as the transmission kernels used for the assessment of the minimum radius of the protection and surveillance zones. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. Here, several recommendations are given on how to increase the effectiveness of some of the sampling procedures. Based on the average length of the period between virus introduction and the reporting of a CSF suspicion, the monitoring period was assessed as non‐effective. In a similar way, it was recommended that the length of the measures in the protection and surveillance zones were increased from 15 to 25 days in the protection zone and from 30 to 40 days in the surveillance zone. Finally, the analysis of existing Kernels for CSF suggested that the radius of the protection and the surveillance zones comprise 99% of the infections from an affected establishment if transmission occurred. Recommendations provided for each of the scenarios assessed aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to CSF.

Abstract The European Commission asked EFSA to provide study designs for the investigation of four research domains (RDs) according to major gaps in knowledge identified by EFSA in a report published in 2019: (RD 1) African swine fever (ASF) epidemiology in wild boar; (RD 2) ASF transmission by vectors; (RD 3) African swine fever virus (ASFV) survival in the environment, and (RD 4) the patterns of seasonality of ASF in wild boar and domestic pigs in the EU. In this Scientific Opinion, the second RD on ASF epidemiology in wild boar is addressed. Twenty‐nine research objectives were proposed by the working group and broader ASF expert networks and 23 of these research objectives met a prespecified inclusion criterion. Fourteen of these 23 research objectives met the predefined threshold for selection and so were prioritised based on the following set of criteria: (1) the impact on ASF management; (2) the feasibility or practicality to carry out the study; (3) the potential implementation of study results in practice; (4) a possible short time‐frame study (< 1 year); (5) the novelty of the study; and (6) if it was a priority for risk managers. Finally, after further elimination of three of the proposed research objectives due to overlapping scope of studies published during the development of this opinion, 11 research priorities were elaborated into short research proposals, considering the potential impact on ASF management and the period of one year for the research activities.