Exploring the effect of clinical case definitions on influenza vaccine effectiveness estimation at primary care level: Results from the end-of-season 2022-23 VEBIS multicentre study in Europe.

BACKGROUND: Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022-23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. METHODS: We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0-14, 15-64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). RESULTS: We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. DISCUSSION: Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022-23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons.

Hospitalization costs in Portugal among people with obesity: results from a nationwide population-based cohort 2011 to 2021.

Background: Obesity has been extensively studied over the years, primarily focusing on the physiological aspects of the disease. However, the general burden of obesity mainly the financial implications and its influence on hospitalization and length of stay have only recently garnered attention in the literature, particularly in the case of Portugal. Aim: This study aimed to investigate the association between obesity and hospitalizations in the Portuguese adult population and compare the average costs of hospitalization among participants with and without obesity. Methods: At baseline, the analytic sample consisted of 10,102 participants aged ≥18 years from the Portuguese population-based Epidemiology of Chronic Diseases Cohort (EpiDoC). Participants were then followed for up to 10 years from 2011 to 2021 in three more waves of data collection. Body mass index was derived from self-reported weight and height, and instances of hospitalization were self-reported by the participants. The associated costs for each hospitalization episode were categorized according to national legislation and valued according to the pricing for Diagnosis Related Groups. Results: Obesity was associated with more hospitalizations (for example, Obesity class I vs. normal weight: OR = 1.33 [1.14-1.55]). However, when the presence of multimorbidity was considered, this association diminished. While longer hospital length of stay was observed in individuals with higher obesity categories, this difference did not reach statistical significance. On average, the total hospitalization costs per patient with obesity amounted to €200.4 per year. Conclusion: Obesity is as a risk factor for hospitalizations and potentially with higher length of stay hospitalizations, with this effect being partially mediated by the concurrent presence of multimorbidity. Consequently, obesity constitutes an additional burden on healthcare systems. This underscores the imperative of implementing cost-effective prevention programs aimed at addressing and managing this significant public health concern.

The mesopontine tegmentum in reward and aversion: from cellular heterogeneity to behaviour.

The mesopontine tegmentum, comprising the pedunculopontine tegmentum (PPN) and the laterodorsal tegmentum (LDT), is intricately connected to various regions of the basal ganglia, motor systems, and limbic systems. The PPN and LDT can regulate the activity of different brain regions of these target systems, and in this way are in a privileged position to modulate motivated behaviours. Despite recent findings, the PPN and LDT have been largely overlooked in discussions about the neural circuits associated with reward and aversion. This review aims to provide a timely and comprehensive resource on past and current research, highlighting the PPN and LDT's connectivity and influence on basal ganglia and limbic, and motor systems. Seminal studies, including lesion, pharmacological, and optogenetic/chemogenetic approaches, demonstrate their critical roles in modulating reward/aversive behaviours. The review emphasizes the need for further investigation into the associated cellular mechanisms, in order to clarify their role in behaviour and contribution for different neuropsychiatric disorders.

Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study.

Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.

Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress.

Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti-AML activity of bortezomib (BTZ), emphasizing its anti-LSC potential, using KG-1a cells, an AML cell line with stem-like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem-like features of KG-1a cells, as observed by the reduction in CD34- and CD123-positive cells. A reduction in NF-κB p65 nuclear staining was observed in BTZ-treated KG-1a cells, in addition to upregulation of the NF-κB inhibitor gene NFΚBIB. BTZ-induced DNA fragmentation, nuclear condensation, cell shrinkage and loss of transmembrane mitochondrial potential along with an increase in active caspase-3 and cleaved PARP-(Asp 214) level in KG-1a cells. Furthermore, BTZ-induced cell death was partially prevented by pretreatment with the pancaspase inhibitor Z-VAD-(OMe)-FMK, indicating that BTZ induces caspase-mediated apoptosis. BTZ also increased mitochondrial superoxide levels in KG-1a cells, and BTZ-induced apoptosis was partially prevented by pretreatment with the antioxidant N-acetylcysteine, indicating that BTZ induces oxidative stress-mediated apoptosis in KG-1a cells. At a dosage of 0.1 mg/kg every other day for 2 weeks, BTZ significantly reduced the percentage of hCD45-positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG-1a cells with tolerable toxicity. Taken together, these data indicate that the anti-LSC potential of BTZ appears to be an important strategy for AML treatment.

ASDAS-CRP and ASDAS-ESR cut-offs for disease activity states in axial spondyloarthritis - Are they interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) is recommended over erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1 and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from axSpA patients initiating a tumour necrosis factor inhibitor from nine European registries. ASDAS-ESR cut-offs were estimated using the Youden index. Level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3,664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9 and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

A prolonged intensive care unit stay defines a worse long-term prognosis - Insights from the critically ill mortality by age (Cimba) study.

BACKGROUND: Patients with critical illness often survive the intensive care unit (ICU) at a cost of prolonged length of stay (LOS) and slow recovery. This chronic critically ill disease may lead to long-term poor outcomes, especially in older or frail patients. OBJECTIVES: The main goal of this study was to address the characteristics and outcomes of patients with prolonged ICU LOS. Mainly, short- and long-term admissions were compared to identify risk factors for persistent critical illness and to characterise the impact on ICU, hospital, and long-term mortality. METHODS: Subanalysis of a retrospective, multicentric, observational study addressing the 2-year outcome of patients admitted to Portuguese ICUs (the Cimba study). Patients were segregated according to an ICU LOS of ≥14 days. RESULTS: Data from 37 118 patients were analysed, featuring a median ICU LOS of 4 days (percentile: 25-75 2-9), and a mortality of 16.1% in the ICU, 24.0% in the hospital, and 38.7% after 2 years. A total of 5334 patients (14.4%) had an ICU LOS of ≥14 days (corresponding to 48.9% of all ICU patients/days). Patients with prolonged LOS were more often younger (52.8% vs 46.4%, were ≤65 years of age , p < 0.001), although more severe (Simplified Acute Physiology Score II: 49.1 ± 16.9 vs 41.8 ± 19.5, p < 0.001), and had higher ICU and hospital mortality (18.3% vs 15.7%, and 31.2 vs 22.8%, respectively). Prolonged ICU LOS was linked to an increased risk of dying during the 2-year follow-up (adjusted Cox proportional hazard: 1.65, p < 0.001). CONCLUSION: Prolonged LOS is associated with a long-term impact on patient prognosis. More careful planning of care should incorporate these data.

Description of an intramonocytic haemoparasite, Hepatozoon lainsoni sp. nov. (Apicomplexa: Adeleorina: Hepatozoidae), infecting Ameiva ameiva lizard (Reptilia: Squamata: Teiidae) in northern Brazil.

Haemogregarine (Apicomplexa: Adeleorina) parasites are considered to be the most common and widespread haemoparasites in reptiles. The genus Hepatozoon (Apicomplexa: Adeleorina: Hepatozoidae) can be found parasitizing a broad range of species and, in reptiles, they infect mainly peripheral blood erythrocytes. The present study detected and characterized a haemogregarine isolated from the lizard species, Ameiva ameiva, collected from the municipality of Capanema, Pará state, north Brazil. Blood smears and imprints from lungs, brain, heart, kidney, liver, bone marrow and spleen were observed using light microscopy and the parasite was genetically identified by molecular analysis. Morphological, morphometric and molecular data were obtained. Parasite gamonts were found in 49.5% (55/111) of the blood smears from A. ameiva, and were characterized as oval, averaging 12.0 ± 0.8 × 5.9 ± 0.6 µm2 in size, which displaced the nuclei of parasitized monocytes laterally. Parasite forms resembling immature gamonts were observed in the spleen and bone marrow of the lizards. Furthermore, phylogenetic analyses of 18S rRNA sequences did not reveal gene similarity with other Hepatozoon spp. sequences from reptiles. Thus, morphological and molecular analyses have identified a new species of Hepatozoon parasite, Hepatozoon lainsoni sp. nov., which infects monocytes of the A. ameiva lizard.

Bulky malignant peripheral nerve sheath tumour of the left thigh in a pregnant woman presenting with a pathological fracture of the proximal femur.

Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft tissue sarcoma with a poor prognosis, affecting most commonly the extremities. The lungs constitute the most frequent location for distant metastases. Half of all MPNSTs arise in patients with neurofibromatosis type 1, while approximately 10% are radiation induced and the rest are sporadic.The authors present a pregnant woman in her 40s with a sporadic MPNST of the lower limb and with lung metastases at diagnosis. Treatment consisted of interilioabdominal amputation, followed by adjuvant chemotherapy. Partial response and disease stabilisation were achieved with chemotherapy.Surgical resection with negative margins is the only potentially curative therapy, while radiation therapy and chemotherapy might be useful in the neoadjuvant or adjuvant setting, but their advantage in survival is not demonstrated. In the reported case, chemotherapy permitted the achievement of partial response and stabilisation of the disease.

Coping and emotions of global higher education students to the Ukraine war worldwide.

Trauma scientists have raised the alarm about the devastating consequences of the Ukraine war on mental health. We examined how higher education students-as indirect victims-coped with this conflict and how they emotionally reacted during 2022. We involved 2314 students from 16 countries through an online survey. A structural equation model indicated significant relations between war-related worry about military and macroeconomics domains and two coping strategies (opposition, support giving), in turn significantly linked with six emotions. The model was strongly invariant across gender, study field, and geographic area. The most frequent emotions were anger and anxiety, followed by two future-centred emotions (hopelessness and hope). Emotions were more frequent for females and students of the countries geographically close to the war region. Our findings call for evidence-based policy recommendations to be implemented by institutions to combat the negative short and long-term psychological sequelae of being witnesses of armed conflicts.

Elastic Liposomes Containing Calcium/Magnesium Ferrite Nanoparticles Coupled with Gold Nanorods for Application in Photothermal Therapy.

This work reports on the design, development, and characterization of novel magneto-plasmonic elastic liposomes (MPELs) of DPPC:SP80 (85:15) containing Mg0.75Ca0.25Fe2O4 nanoparticles coupled with gold nanorods, for topical application of photothermal therapy (PTT). Both magnetic and plasmonic components were characterized regarding their structural, morphological, magnetic and photothermal properties. The magnetic nanoparticles display a cubic shape and a size (major axis) of 37 ± 3 nm, while the longitudinal and transverse sizes of the nanorods are 46 ± 7 nm and 12 ± 1.6 nm, respectively. A new methodology was employed to couple the magnetic and plasmonic nanostructures, using cysteine as bridge. The potential for photothermia was evaluated for the magnetic nanoparticles, gold nanorods and the coupled magnetic/plasmonic nanoparticles, which demonstrated a maximum temperature variation of 28.9 °C, 33.6 °C and 37.2 °C, respectively, during a 30 min NIR-laser irradiation of 1 mg/mL dispersions. Using fluorescence anisotropy studies, a phase transition temperature (Tm) of 35 °C was estimated for MPELs, which ensures an enhanced fluidity crucial for effective crossing of the skin layers. The photothermal potential of this novel nanostructure corresponds to a specific absorption rate (SAR) of 616.9 W/g and a maximum temperature increase of 33.5 °C. These findings point to the development of thermoelastic nanocarriers with suitable features to act as photothermal hyperthermia agents.

Change in Age profile of Respiratory Syncytial Virus disease over the course of annual epidemics: a multi-national study.

OBJECTIVES: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics. METHODS: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season. RESULTS: In all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to 6 months. CONCLUSIONS: The age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines.

Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells.

Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N-acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.

Dying with end stage kidney disease: factors associated with place of death on a palliative care program / Fim de vida na doença renal terminal: fatores associados ao local de óbito num programa de cuidados paliativos

Abstract Introduction: End of life care of patients with end-stage kidney disease (ESKD) may be particularly challenging and requires the intervention of a specialized palliative care team (PCT). Objective: To characterize the population of ESKD patients referred to a PCT and evaluate the determinants of planned dying at home. Methods: We performed a retrospective observational cohort study of all patients with ESKD referred to our PCT between January 2014 and December 2021 (n = 60) and further characterized those with previously known ESKD regarding place of death (n = 53). Results: The majority of the patients were female and the median age was 84 years. Half of the patients were on conservative treatment, 43% were on chronic hemodialysis, and the remainder underwent hemodialysis on a trial basis and were subsequently suspended. Of those with previously known ESKD, 18% died at home and neither gender, age, cognition, performance status, comorbidities, CKD etiology, or treatment modality were associated with place of death. Anuria was significantly associated with dying at the hospital as was shorter time from dialysis suspension and death. Although not reaching statistical significance, we found a tendency towards a longer duration of palliative care follow-up in those dying at home. Conclusion: Dying at home is possible in a palliative domiciliary program regardless of age, gender, etiology of CKD, major comorbidities, and treatment modality. Anuria and shorter survival from RRT withdrawal may be limiting factors for planned dying at home. A longer follow-up by palliative care may favor dying at home.

Resumo Introdução: Os cuidados de fim de vida em doentescom doença renal terminal (DRT) podem ser desafiantes e necessitar do apoio de uma equipa especializada em cuidados paliativos (ECP). Objetivo: Caracterizar a população de doentes com DRT encaminhada à ECP e avaliar os determinantes para um fim de vida planeado no domicílio. Métodos: Realizámos um estudo de coorte observacional retrospectivo dos doentes com DRT encaminhados à ECP entre janeiro/2014 e dezembro/2021 (n = 60) e caracterizámos aqueles com DRT previamente conhecida relativamente ao local de fim de vida (n = 53). Resultados: A maioria dos pacientes eram mulheres comidade mediana de 84 anos. Metade dos doentes encontrava-se em tratamento conservador, 43% em hemodiálise crónica e os restantes suspenderam diálise iniciada agudamente. Daqueles com DRT previamente conhecida, 18% morreram em casa. Não foi objetivada associação entre género, idade, cognição, status funcional, comorbilidades, etiologia da DRC ou modalidade de tratamento da DRT e o local de óbito. A anúria e a menor sobrevida após suspensão de diálise associaram-se a um fim de vida no hospital e verificámos uma tendência para o fim de vida em casa nos doentes com mais tempo de acompanhamento pela ECP. Conclusão: O fim de vida no domicílio é possível num programa domiciliário de cuidados paliativos, independentemente de idade, sexo, etiologia da DRC, principais comorbilidades e modalidade de tratamento. A anúria e o menor tempo de sobrevida após suspensão da TRS podem ser fatores limitantes. Um acompanhamento mais longo em cuidados paliativos pode favorecer o fim de vida no domicílio.

Glial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablation.

Adult cytogenesis, the continuous generation of newly-born neurons (neurogenesis) and glial cells (gliogenesis) throughout life, is highly impaired in several neuropsychiatric disorders, such as Major Depressive Disorder (MDD), impacting negatively on cognitive and emotional domains. Despite playing a critical role in brain homeostasis, the importance of gliogenesis has been overlooked, both in healthy and diseased states. To examine the role of newly formed glia, we transplanted Glial Restricted Precursors (GRPs) into the adult hippocampal dentate gyrus (DG), or injected their secreted factors (secretome), into a previously validated transgenic GFAP-tk rat line, in which cytogenesis is transiently compromised. We explored the long-term effects of both treatments on physiological and behavioral outcomes. Grafted GRPs reversed anxiety-like deficits and demonstrated an antidepressant-like effect, while the secretome promoted recovery of only anxiety-like behavior. Furthermore, GRPs elicited a recovery of neurogenic and gliogenic levels in the ventral DG, highlighting the unique involvement of these cells in the regulation of brain cytogenesis. Both GRPs and their secretome induced significant alterations in the DG proteome, directly influencing proteins and pathways related to cytogenesis, regulation of neural plasticity and neuronal development. With this work, we demonstrate a valuable and specific contribution of glial progenitors to normalizing gliogenic levels, rescuing neurogenesis and, importantly, promoting recovery of emotional deficits characteristic of disorders such as MDD.

Evolution of attack in handball when playing 7 vs. 6 with empty goal between 2020 and 2023: coaches' perception vs. observational results.

Introduction: Recently, several studies on the 7 vs. 6 "empty goal" (EG) in handball have produced different and even contradictory results. The aim of the present study was to investigate the behavior of teams and players in the 7 vs. 6 EG attack in the European (Euro) and World Championships (WCh) between 2020 and 2023 and characterize the coaches' perceptions. Methods: A mixed-methods approach was used, consisting of the following: (i) an observational methodology and instrument developed and validated to collect observational data on player and team behavior; and (ii) a developed and validated questionnaire to coaches on their perceptions of the 7 vs. 6 game. Observational data were collected during the Euro 2020 and 2022 games (n = 62) and the WCh 2021 and 2023 games (n = 70). A total of 132 games and 391 situations of 7 vs. 6 attacking sequences were observed. In total, 156 coaches participated (146 men), with a mean age 42.33 ± 11.87 years, 19 nationalities, and with 12.77 ± 9.45 years of experience. Results and discussion: The choice of 7 vs. 6 offensive play was mostly made in the second half (>73%). The effectiveness of 7 vs. 6 offensive sequences was higher in the top six teams than in the team's ranked 7th to 12th (Euro 2020 51.6%-50.0%; WCh 2021 52.0%-50.0%; Euro 2022 53.1%-41.7%; WCh 2023 50.0%-43.8%). Some patterns of association were found (p < 0.05 and with values >±1.96): (i) scoring a goal with a breakthrough shot was significantly associated with the effectiveness of the 7 vs. 6 attack (Euro 2020 2.61; WCh 2021 2.87; Euro 2022 2.68; WCh 2023 2.32); (ii) teams in the top six significantly used 7 vs. 6 when they were winning (Euro 2020 2.17; WCh 2021 3.52; Euro 2022 5.88; WCh 2023 2.54); and (iii) teams in the bottom six used it when they were losing by at least four goals (Euro 2020 7.56; Euro 2022 6.64; WCh 2023 4.37) or when they were winning by four goals or more (WCh 2021 2.58). Coaches that agree with the possibility of playing 7 vs. 6 (74.4%), rarely or never do so (55.6%) because it brings little or no advantage (52.6%). The results of the analysis confirmed the perception of the coaches, the low use of 7 vs. 6, the low advantage associated with it, and the influence of the result and the moment of the game on its use.

COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.