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Abstract Background In vitro cultivation of Plasmodium falciparum is usually carried out through the continuous preservation of infected erythrocytes deposited in static thin layers of settled haematocrit. This technique, called the candle-jar method, was first achieved by Trager and Jensen in 1976 and has undergone slight modifications since then. However, no systematic studies concerning the geometry of the haematocrit layer have been carried out. In this work, a thorough investigation of the effects of the geometric culturing conditions on the parasite's development is presented. Methods Several experimental trials exploring different settings have been carried out, covering haematocrit layer depths that ranged from 6 mm to 3 mm and separation between the walls of the culturing device that ranged from 7.5 mm to 9 mm. The obtained results have been analysed and compared to different system-level models and to an Individual-Based Model. Conclusion In line with the results, a mechanism governing the propagation of the infection which limits it to the vicinity of the interface between the haematocrit layer and the culture medium is deduced, and the most appropriate configurations are proposed for further experimental assays.

Responds to a critique of the authors' article 'Disposition of Oxytetracycline in Pigs After I.M. Administration of Two Long-Acting Formulations. Criticism that the study is only routine bioequivalence with only commercial interests; Aims of the study; Parameters studied.

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6 months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0-6 months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11 m-old with respect to 12-35 m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11 m-old and 12-35 m-old with respect to the > 35 m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11 m-old RR (95% CI) of RSV infection incidence for > 35 m-old was 1.7 (1.5-2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6-9.9), 8.8 (6.9-11.3), and 7.1 (5.7-8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11 m-old group compared to the 12-35 m-old, the pre-pandemic (2014/2015-2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2-9.6) and 6.0 (5.7-6.2), respectively, significantly higher than the RR of 3.6 (3.4-3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11 m-old compared to > 35 m-old has been reduced by 75.6% (73.4-77.5) in last season, and the risk for all-causes bronchiolitis for 12-35 m-old by 61.9% (60.9-62.9) from the pre-pandemic period and by 39.8% (39.3-40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6 months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using.   primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11 m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%., (© 2024. The Author(s).)

Introduction: This study aims to investigate the relationship between deprivation, as measured by a socioeconomic deprivation index (SDI) score for census tract urban areas, and COVID-19 infections and vaccine uptake among children and adolescents before and after the vaccination rollout in Catalonia, Spain., Methods: We conducted a population-based cohort study using primary care records. Individuals were followed 3 months before the start of the vaccination campaign in Spain and 3 months after. Children (5-11 years) and adolescents (12-15 years) with at least 1 year of prior history observation available and without missing deprivation data. For each outcome, we estimated cumulative incidence and crude Cox proportional-hazard models by SDI quintiles, and hazard ratios (HRs) of COVID-19 infection and vaccine uptake relative to the least deprived quintile, Q1., Results: Before COVID-19 vaccination rollout, 290,625 children and 179,685 adolescents were analyzed. Increased HR of deprivation was associated with a higher risk of COVID-19 infection in both children [Q5: 1.55 (95% CI, 1.47-1.63)] and adolescents [Q5: 1.36 (95% CI, 1.29-1.43)]. After the rollout, this pattern changed among children, with lower risk of infection in more deprived areas [Q5: 0.62 (95% CI, 0.61-0.64)]. Vaccine uptake was higher among adolescents than children, but in both age groups, non-vaccination was more common among those living in more deprived areas (39.3% and 74.6% in Q1 vs. 26.5% and 66.9% in Q5 among children and adolescents, respectively)., Conclusions: Children and adolescents living in deprived areas were at higher risk of COVID-19 non-vaccination. Socioeconomic disparities in COVID-19 infection were also evident before vaccine rollout, with a higher infection risk in deprived areas across age groups. Our findings suggest that changes in the association between deprivation and infections among children after the vaccine rollout were likely due to testing disparities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 López-Sánchez, Perramon-Malavez, Soriano-Arandes, Prats, Duarte-Salles, Raventós and Roel.)

Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25-85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors., Competing Interests: Competing interests DPA’s department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA’s department. The views expressed in this study are the personal views of MGM and do not represent the views of her current employer, the European Medicines Agency. All other authors declare no conflicts of interest. Ethics approval & consent to participate All participants provided informed consent to participate in each one of the GWAS we have used. UK Biobank received ethical approval from the North West Multi-centre Research Ethics Committee (REC reference: 16/NW/0274). All participants provided informed consent to participate., (© 2024. The Author(s).)

Addition of molecular data to prognostic models has improved risk stratification of myelodysplastic neoplasms (MDS). However, the role of molecular lesions, particularly in the group of low-risk disease (LR-MDS), is uncertain. We evaluated a set of 227 patients with LR-MDS. Overall survival (OS) and probability of leukaemic progression were the main endpoints. RUNX1 was associated with lower OS and SF3B1 with a reduced risk of death (HR: 1.7, 95% CI, 1.1-2.9; p = 0.05; and HR: 0.23, 95% CI 0.1-0.5; p < 0.001; respectively). TP53 and RUNX1 mutations were predictive covariates for the probability of leukaemic progression (p < 0.001). Blast percentage, neither analysed as categorical (<5% vs. 5%-9%; HR: 1.3, 95% CI, 0.7-2.9; p = 0.2) nor as a continuous variable (HR: 1.07, 95% CI, 0.9-1.1; p = 0.07), had impact on survival or probability of progression (sHR: 1.05, 95% CI, 0.9-1.1; p = 0.2). These results retained statistical significance when analysis was restricted to the definition of LR-MDS according to the WHO 2022 and ICC classifications (<5% blasts). Thus, with the incorporation of molecular data, blast percentage happens to lose clinical significance both for survival and probability of progression in the group of patients with LR-MDS., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Research benefits from the incorporation of patient-important outcomes. We interviewed individuals after a critical illness during pregnancy to identify outcomes for the development of a core outcome set (COS)., Methods: Participants were identified through intensive care unit (ICU) admissions in Toronto, Canada, and Barranquilla, Colombia. Interviewers used a semi-structured guide, and discussions were recorded and transcribed. Transcripts underwent inductive thematic analysis to delineate themes and patient-important outcomes., Results: Twelve individuals were interviewed. Twenty-six patient-important outcomes were elicited, which represented the core outcome areas of mortality ( n  = 1), physiological/clinical outcomes ( n  = 7), functioning and life impact ( n  = 13), resource use ( n  = 4) and adverse events ( n  = 1). These related to five identified themes of mental well-being, quality of care delivered, clinicians' communication, regaining functional independence and mother-newborn separation., Conclusions: This qualitative study identified patient-important outcomes from persons with lived experience of critical illness in pregnancy which will inform the development of a COS., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Aim: High-resolution respirometry in human permeabilized muscle fibers is extensively used for analysis of mitochondrial adaptions to nutrition and exercise interventions, and is linked to athletic performance. However, the lack of standardization of experimental conditions limits quantitative inter- and intra-laboratory comparisons., Methods: In our study, an international team of investigators measured mitochondrial respiration of permeabilized muscle fibers obtained from three biopsies (vastus lateralis) from the same healthy volunteer to avoid inter-individual variability. High-resolution respirometry assays were performed together at the same laboratory to assess whether the heterogenity in published results are due to the effects of respiration media (MiR05 versus Z) with or without the myosin inhibitor blebbistatin at low- and high-oxygen regimes., Results: Our findings reveal significant differences between respiration media for OXPHOS and ETcapacities supported by NADH&succinate-linked substrates at different oxygen concentrations. Respiratory capacities were approximately 1.5-fold higher in MiR05 at high-oxygen regimes compared to medium Z near air saturation. The presence or absence of blebbistatin in human permeabilized muscle fiber preparations was without effect on oxygen flux., Conclusion: Our study constitutes a basis to harmonize and establish optimum experimental conditions for respirometric studies of permeabilized human skeletal muscle fibers to improve reproducibility., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of a pharmaceutical intervention on treatment optimization in patients with type 2 diabetes mellitus., Design: Before-after intervention study. SITE: Health centers of the Primary Care Department of Camp de Tarragona., Participants: Patients aged ≥ 18 years, diagnosed with type 2 diabetes mellitus and under treatment with antidiabetic drugs., Interventions: Review of pharmacological treatment for type 2 diabetes mellitus and issuance of proposals for its adequacy., Main Measurements: Demographic and clinical variables were collected to assess the adequacy of antidiabetic treatment. A consensus meeting was arranged with the patients' primary care physician to evaluate the proposals for improvement. The implementation of the proposals and the variation in postintervention glycemic control were assessed., Results: A total of 907 patients (59% men) were included. A total of 782 proposals for intervention were made in 65.8% of the patients reviewed. Of the proposals, 43.5% corresponded to drug discontinuation, 16% to intensification of dosing and 12.6% to exchange for a therapeutic equivalent. Of the consensual proposals, 54.7% were implemented. HbA1c was reduced by 0.2% after the intervention (7.4 vs 7.2%)., Conclusions: Review of the pharmacological treatment of patients with type 2 diabetes mellitus by a pharmacist or pharmacologist facilitates its optimization., (Copyright © 2024 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Background: In Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab's effectiveness across primary and hospital care outcomes., Methods: Retrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome-RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis-death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs., Results: Among 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection., Conclusion: We demonstrated nirsevimab's effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns., Competing Interests: Competing interests: AS-A has received an honorarium for attending scientific meetings from Sanofi, MSD and Pfizer. VP has received an honorarium for attending scientific meetings from Sanofi and Pfizer. AA has received sponsorship from Sanofi to attend scientific meetings., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The limited available data suggest that the Canadian surgical workforce does not reflect the racial diversity of the patient population it serves, despite the well-established benefits of patient-provider race concordance. There have been no studies to date that characterize the systemic and individual challenges faced by Black medical students in matching to and successfully finishing training in a surgical specialty within a Canadian context that can explain this underrepresentation., Study Design: Using critical qualitative inquiry and purposive sampling to ensure sex, geographical, and student or trainee year heterogeneity, we recruited self-identifying Black medical students and surgical residents across Canada. Online in-depth semistructured interviews were conducted and transcribed verbatim. Transcripts were analyzed through an inductive reflexive narrative thematic process by 4 analysts., Results: Twenty-seven participants including 18 medical students and 9 residents, were interviewed. The results showed 3 major themes that characterized their experiences: journey to and through medicine, perceptions of the surgical culture, and recommendations to improve the student experience. Medical students identified lack of mentorship and representation as well as experiences with racism as the main barriers to pursuing surgical training. Surgical trainees cited systemic racism, lack of representation, and insufficient safe spaces as the key deterrents to program completion. The intersection with sex exponentially increased these identified barriers., Conclusions: Except for a few surgical programs, medical schools across Canada do not offer a safe space for Black students and trainees to access and complete surgical training. An urgent change is needed to provide diverse mentorship that is transparent, acknowledges the real challenges related to systemic racism and biases, and is inclusive of different racial and ethnic backgrounds., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: People experiencing homelessness and marginalization face considerable barriers to accessing healthcare services. Increased reliance on technology within healthcare has exacerbated these inequities. We evaluated a hospital-based prescription phone program aimed to reduce digital health inequities and improve access to services among marginalized patients in Emergency Departments. We examined the perceived outcomes of the program and the contextual barriers and facilitators affecting outcomes., Methods: We conducted a constructivist qualitative program evaluation at two urban, academic hospitals in Toronto, Ontario. We interviewed 12 healthcare workers about their perspectives on program implementation and outcomes and analyzed the interview data using reflexive thematic analysis., Results: Our analyses generated five interrelated program outcomes: building trust with patients, facilitating independence in healthcare, bridging sectors of care, enabling equitable care for marginalized populations, and mitigating moral distress among healthcare workers. Participants expressed that phone provision is critical for adequately serving patients who face barriers to accessing health and social services, and for supporting healthcare workers who often lack resources to adequately serve these patients. We identified key contextual enablers and challenges that may influence program outcomes and future implementation efforts., Conclusions: Our findings suggest that providing phones to marginalized patient populations may address digital and social health inequities; however, building trusting relationships with patients, understanding the unique needs of these populations, and operating within a biopsychosocial model of health are key to program success., (© 2024. The Author(s).)

Objectives: Parents' decisions to vaccinate their children against COVID-19 are complex and often informed by discussions with primary care physicians. However, little is known about physicians' perspectives on COVID-19 vaccinations for children or their experiences counselling parents in their decision-making. We explored physicians' experiences providing COVID-19 vaccination recommendations to parents and their reflections on the contextual factors that shaped these experiences., Design: We conducted an interpretive qualitative study using in-depth interviews. We analyzed the data using reflexive thematic analysis and a socioecological framework., Setting: This study involved primary care practices associated with The Applied Research Group for Kids (TARGet Kids!) primary care research network in the Greater Toronto Area, Ontario, Canada., Participants: Participants were 10 primary care physicians, including family physicians, paediatricians and paediatric subspecialists., Results: Participants discussed elements at the individual level (their identity, role, and knowledge), the interpersonal level (their relationships with families, responsiveness to parents' concerns, and efforts to build trust) and structural level (contextual factors related to the evolving COVID-19 climate, health system pandemic response, and constraints on care delivery) that influenced their experiences providing recommendations to parents. Our findings illustrated that physicians' interactions with families were shaped by a confluence of their own perspectives, their responses to parents' perspectives, and the evolving landscape of the broader pandemic., Conclusions: Our study underscores the social and relational nature of vaccination decision-making and highlights the multiple influences on primary care physicians' experiences providing COVID-19 vaccination recommendations to parents. Our findings offer suggestions for future COVID-19 vaccination programmes for children. Delivery of new COVID-19 vaccinations for children may be well suited within primary care offices, where trusting relationships are established, but physicians need support in staying knowledgeable about emerging information, communicating available evidence to parents to inform their decision-making and dedicating time for vaccination counselling., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In a clinical context, conventional optical microscopy is commonly used for the visualization of biological samples for diagnosis. However, the availability of molecular techniques and rapid diagnostic tests are reducing the use of conventional microscopy, and consequently the number of experienced professionals starts to decrease. Moreover, the continuous visualization during long periods of time through an optical microscope could affect the final diagnosis results due to induced human errors and fatigue. Therefore, microscopy automation is a challenge to be achieved and address this problem. The aim of the study is to develop a low-cost automated system for the visualization of microbiological/parasitological samples by using a conventional optical microscope, and specially designed for its implementation in resource-poor settings laboratories. A 3D-prototype to automate the majority of conventional optical microscopes was designed. Pieces were built with 3D-printing technology and polylactic acid biodegradable material with Tinkercad/Ultimaker Cura 5.1 slicing softwares. The system's components were divided into three subgroups: microscope stage pieces, storage/autofocus-pieces, and smartphone pieces. The prototype is based on servo motors, controlled by Arduino open-source electronic platform, to emulate the X-Y and auto-focus (Z) movements of the microscope. An average time of 27.00 ± 2.58 seconds is required to auto-focus a single FoV. Auto-focus evaluation demonstrates a mean average maximum Laplacian value of 11.83 with tested images. The whole automation process is controlled by a smartphone device, which is responsible for acquiring images for further diagnosis via convolutional neural networks. The prototype is specially designed for resource-poor settings, where microscopy diagnosis is still a routine process. The coalescence between convolutional neural network predictive models and the automation of the movements of a conventional optical microscope confer the system a wide range of image-based diagnosis applications. The accessibility of the system could help improve diagnostics and provide new tools to laboratories worldwide., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dantas de Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service-oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world., (© 2024 The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.)

Acute respiratory viral infections pose a significant healthcare burden on the pediatric population globally, but data on the dissemination pattern in the community due to the COVID-19 pandemic are scarce. We conducted a two-year prospective multicenter study in Catalonia (Spain) that examined the prevalence and coinfection dynamics of respiratory viruses among 1276 pediatric patients from different age groups attending primary care. Coinfection analysis demonstrated complex patterns and revealed a coinfection rate of 23.8% for SARS-CoV-2, often in association with rhinovirus or influenza A. This study provides valuable data to understand post-pandemic viral interactions, which is imperative for public health interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants., Materials and Methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility  ( Δ β )   between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants., Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated Δ β between variants, revealing that: ( i ) Δ β increased progressively from the Alpha to the Omicron variant; ( i i ) Δ β showed a high degree of variability within Omicron variants; ( i i i ) a higher Δ β was associated with a later emergence of the variant within a country; ( i v ) a higher degree of immunization of the population against previous variants was associated with a higher Δ β for the Delta variant; ( v ) larger countries exhibited smaller Δ β ,  suggesting regionally diverse outbreaks within the same country; and finally ( v i ) the model reliably captures the dynamics of competing variants, even in complex scenarios., Conclusion: The use of mathematical models allows for precise and reliable estimation of daily cases of each variant. By quantifying Δ β ,  we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. Additionally, we have shown that the geographical characteristics of a country, as well as the timing of new variant entrances, can explain some of the observed differences in variant substitution dynamics across countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 de Rioja, Perramon-Malavez, Alonso, Andrés, Antón, Bordoy, Càmara, Cardona, Català, López, Martí, Martró, Saludes, Prats and Alvarez-Lacalle.)

Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two-three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1-2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%., (© 2024. The Author(s).)

In the current COVID-19 landscape dominated by Omicron subvariants, understanding the timing and efficacy of vaccination against emergent lineages is crucial for planning future vaccination campaigns, yet detailed studies stratified by subvariant, vaccination timing, and age groups are scarce. This retrospective study analyzed COVID-19 cases from December 2021 to January 2023 in Catalonia, Spain, focusing on vulnerable populations affected by variants BA.1, BA.2, BA.5, and BQ.1 and including two national booster campaigns. Our database includes detailed information such as dates of diagnosis, hospitalization and death, last vaccination, and cause of death, among others. We evaluated the impact of vaccination on disease severity by age, variant, and vaccination status, finding that recent vaccination significantly mitigated severity across all Omicron subvariants, although efficacy waned six months post-vaccination, except for BQ.1, which showed more stable levels. Unvaccinated individuals had higher hospitalization and mortality rates. Our results highlight the importance of periodic vaccination to reduce severe outcomes, which are influenced by variant and vaccination timing. Although the seasonality of COVID-19 is uncertain, our analysis suggests the potential benefit of annual vaccination in populations >60 years old, probably in early fall, if COVID-19 eventually exhibits a major peak similar to other respiratory viruses.

Objective: To study the association between COVID-19 vaccination and the risk of post-COVID-19 cardiac and thromboembolic complications., Methods: We conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the UK, Spain and Estonia. Vaccine rollout was grouped into four stages with predefined enrolment periods. Each stage included all individuals eligible for vaccination, with no previous SARS-CoV-2 infection or COVID-19 vaccine at the start date. Vaccination status was used as a time-varying exposure. Outcomes included heart failure (HF), venous thromboembolism (VTE) and arterial thrombosis/thromboembolism (ATE) recorded in four time windows after SARS-CoV-2 infection: 0-30, 31-90, 91-180 and 181-365 days. Propensity score overlap weighting and empirical calibration were used to minimise observed and unobserved confounding, respectively.Fine-Gray models estimated subdistribution hazard ratios (sHR). Random effect meta-analyses were conducted across staggered cohorts and databases., Results: The study included 10.17 million vaccinated and 10.39 million unvaccinated people. Vaccination was associated with reduced risks of acute (30-day) and post-acute COVID-19 VTE, ATE and HF: for example, meta-analytic sHR of 0.22 (95% CI 0.17 to 0.29), 0.53 (0.44 to 0.63) and 0.45 (0.38 to 0.53), respectively, for 0-30 days after SARS-CoV-2 infection, while in the 91-180 days sHR were 0.53 (0.40 to 0.70), 0.72 (0.58 to 0.88) and 0.61 (0.51 to 0.73), respectively., Conclusions: COVID-19 vaccination reduced the risk of post-COVID-19 cardiac and thromboembolic outcomes. These effects were more pronounced for acute COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough versus unvaccinated SARS-CoV-2 infection., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The first hematopoietic stem and progenitor cells (HSPCs) emerge in the Aorta-Gonad-Mesonephros (AGM) region of the mid-gestation mouse embryo. However, the precise nature of their supportive mesenchymal microenvironment remains largely unexplored. Here, we profiled transcriptomes of laser micro-dissected aortic tissues at three developmental stages and individual AGM cells. Computational analyses allowed the identification of several cell subpopulations within the E11.5 AGM mesenchyme, with the presence of a yet unidentified subpopulation characterized by the dual expression of genes implicated in adhesive or neuronal functions. We confirmed the identity of this cell subset as a neuro-mesenchymal population, through morphological and lineage tracing assays. Loss of function in the zebrafish confirmed that Decorin, a characteristic extracellular matrix component of the neuro-mesenchyme, is essential for HSPC development. We further demonstrated that this cell population is not merely derived from the neural crest, and hence, is a bona fide novel subpopulation of the AGM mesenchyme., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Introduction: We use Spanish data from August 2020 to March 2021 as a natural experiment to analyze how a standardized measure of COVID-19 growth correlates with asymmetric meteorological and mobility situations in 48 Spanish provinces. The period of time is selected prior to vaccination so that the level of susceptibility was high, and during geographically asymmetric implementation of non-pharmacological interventions., Methods: We develop reliable aggregated mobility data from different public sources and also compute the average meteorological time series of temperature, dew point, and UV radiance in each Spanish province from satellite data. We perform a dimensionality reduction of the data using principal component analysis and investigate univariate and multivariate correlations of mobility and meteorological data with COVID-19 growth., Results: We find significant, but generally weak, univariate correlations for weekday aggregated mobility in some, but not all, provinces. On the other hand, principal component analysis shows that the different mobility time series can be properly reduced to three time series. A multivariate time-lagged canonical correlation analysis of the COVID-19 growth rate with these three time series reveals a highly significant correlation, with a median R-squared of 0.65. The univariate correlation between meteorological data and COVID-19 growth is generally not significant, but adding its two main principal components to the mobility multivariate analysis increases correlations significantly, reaching correlation coefficients between 0.6 and 0.98 in all provinces with a median R-squared of 0.85. This result is robust to different approaches in the reduction of dimensionality of the data series., Discussion: Our results suggest an important effect of mobility on COVID-19 cases growth rate. This effect is generally not observed for meteorological variables, although in some Spanish provinces it can become relevant. The correlation between mobility and growth rate is maximal at a time delay of 2-3 weeks, which agrees well with the expected 5?10 day delays between infection, development of symptoms, and the detection/report of the case., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Conesa, López de Rioja, Gullón, Tauste Campo, Prats, Alvarez-Lacalle and Echebarria.)

Background: ATDOM is the Catalan home healthcare program at primary care level. Patients in the home care program are usually frail, elderly people with multiple comorbidities. They are often polymedicated, leading to a high risk of drug-related problems (DRPs). Our hypothesis is that the pharmacist-led individualized review of the pharmacotherapeutic plans of ATDOM patients will be effective in improving the quality of treatments by reducing DRPs in terms of indication, adequacy, effectiveness, and safety., Methods: Aim: To compare the effectiveness of a standardized pharmaceutical intervention for the review and optimization of pharmacological treatments in ATDOM patients with usual management practice., Design: Pragmatic randomized clinical trial with a comparable control group, with prospective follow-up regarding the intervention on the adequacy of the pharmacological treatment of patients in the ATDOM program., Setting: Primary care teams in the Camp de Tarragona Primary Care Area, Tarragona, Spain., Participants: Four hundred and thirty-two ATDOM patients will be recruited, those who are over 65 years old and who are currently undergoing pharmacological treatment., Measures: Effectiveness of a six-month long intervention in reducing DRPs per patient and polypharmacy. Additionally, in the intervention group we will evaluate the implementation of the proposals for change or improvement made by the responsible physician., Analysis: The outcomes will be analyzed on an intent-to-treat basis and the analysis units will be the individual patients. Logistic regression and linear regression models will be used to evaluate the effects of the intervention on dichotomous and continuous variables versus the control arm., Ethics: The protocol was approved by the Research Ethics Committee of the Jordi Gol Primary Care Research Institute (IDIAPJGol), Barcelona, (19/141-P)., Discussion: If the results of the pharmaceutical intervention are favorable, widespread implementation of the program could be possible. It could be extended to all ATDOM patients or outpatients in general. Interdisciplinary teamwork could be strengthened as a result, which would improve the healthcare continuum., Trial Registration: Retrospectively registered., Clinicaltrials: gov Identifier NCT05820945; Registered 21 March, 2023., (© 2024. The Author(s).)

Introduction: Bronchiolitis, mostly caused by Respiratory Syncytial Virus (RSV), and influenza among other respiratory infections, lead to seasonal saturation at healthcare centers in temperate areas. There is no gold standard to characterize the stages of epidemics, nor the risk of respiratory infections growing. We aimed to define a set of indicators to assess the risk level of respiratory viral epidemics, based on both incidence and their short-term dynamics, and considering epidemical thresholds., Methods: We used publicly available data on daily cases of influenza for the whole population and bronchiolitis in children <2 years from the Information System for Infection Surveillance in Catalonia (SIVIC). We included a Moving Epidemic Method (MEM) variation to define epidemic threshold and levels. We pre-processed the data with two different nowcasting approaches and performed a 7-day moving average. Weekly incidences (cases per 10 5 population) were computed and the 5-day growth rate was defined to create the effective potential growth (EPG) indicator. We performed a correlation analysis to define the forecasting ability of this index., Results: Our adaptation of the MEM method allowed us to define epidemic weekly incidence levels and epidemic thresholds for bronchiolitis and influenza. EPG was able to anticipate daily 7-day cumulative incidence by 4-5 (bronchiolitis) or 6-7 (influenza) days., Discussion: We developed a semi-empirical risk panel incorporating the EPG index, which effectively anticipates surpassing epidemic thresholds for bronchiolitis and influenza. This panel could serve as a robust surveillance tool, applicable to respiratory infectious diseases characterized by seasonal epidemics, easy to handle for individuals lacking a mathematical background., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Perramon-Malavez, Bravo, López de Rioja, Català, Alonso, Álvarez-Lacalle, López, Soriano-Arandes and Prats.)

Objectives: Despite growing evidence suggesting increased COVID-19 mortality among people from ethnic minorities, little is known about milder forms of SARS-CoV-2 infection. We sought to explore the association between ethnic background and the probability of testing, testing positive, hospitalisation, COVID-19 mortality and vaccination uptake., Design: A multistate cohort analysis. Participants were followed between 8 April 2020 and 30 September 2021., Setting: The UK Biobank, which stores medical data on around half a million people who were recruited between 2006 and 2010., Participants: 405 541 subjects were eligible for analysis, limited to UK Biobank participants living in England. 23 891 (6%) of participants were non-white., Primary and Secondary Outcome Measures: The associations between ethnic background and testing, testing positive, hospitalisation and COVID-19 mortality were studied using multistate survival analyses. The association with single and double-dose vaccination was also modelled. Multistate models adjusted for age, sex and socioeconomic deprivation were fitted to estimate adjusted HRs (aHR) for each of the multistate transitions., Results: 18 172 (4.5%) individuals tested positive, 3285 (0.8%) tested negative and then positive, 1490 (6.9% of those tested positive) were hospitalised, and 129 (0.6%) tested positive at the moment of hospital admission (ie, direct hospitalisation). Finally, 662 (17.4%) died after admission. Compared with white participants, Asian participants had an increased risk of negative to positive transition (aHR 1.24 (95% CI 1.02 to 1.52)), testing positive (95% CI 1.44 (1.33 to 1.55)) and direct hospitalisation (1.61 (95% CI 1.28 to 2.03)). Black participants had an increased risk of hospitalisation following a positive test (1.71 (95% CI 1.29 to 2.27)) and direct hospitalisation (1.90 (95% CI 1.51 to 2.39)). Although not the case for Asians (aHR 1.00 (95% CI 0.98 to 1.02)), black participants had a reduced vaccination probability (0.63 (95% CI 0.62 to 0.65)). In contrast, Chinese participants had a reduced risk of testing negative (aHR 0.64 (95% CI 0.57 to 0.73)), of testing positive (0.40 (95% CI 0.28 to 0.57)) and of vaccination (0.78 (95% CI 0.74 to 0.83))., Conclusions: We identified inequities in testing, vaccination and COVID-19 outcomes according to ethnicity in England. Compared with whites, Asian participants had increased risks of infection and admission, and black participants had almost double hospitalisation risk, and a 40% lower vaccine uptake., Competing Interests: Competing interests: DP-A’s research group has received grant support from Amgen, Chesi-Taylor, Novartis and UCB Biopharma. His department has received advisory or consultancy fees from Amgen, Astellas, AstraZeneca, Johnson and Johnson, and UCB Biopharma and fees for speaker services from Amgen and UCB Biopharma. Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DP-A's department and open for external participants organised by his department outside submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Despite antiviral agents that can cure the disease, many individuals with Hepatitis C Virus (HCV) remain untreated. Primary care clinicians can play an important role in HCV treatment but often feel they do not have the requisite skills., Methods: We implemented a population-based improvement intervention over 10 months to support treatment of HCV in a primary care setting. The intervention included a decision-support tool, education for clinicians, enhanced interprofessional team supports, mentorship, and proactive patient outreach. We used process and outcome measures to understand the impact on the proportion of patients who initiated treatment and achieved Sustained Virologic Response (SVR). We used physician focus groups and pharmacist interviews to understand the context and mechanisms influencing the impact of the intervention., Results: Between December 2018 and June 2020, the percentage of HCV RNA positive patients who started treatment rose from 66.0% (354/536) to 75.5% (401/531) with 92.5% (371/401) of those starting treatment achieving SVR. Qualitative findings highlighted that the intervention helped raise awareness and confidence among physicians for treating HCV in primary care. A collaborative team environment, education, mentorship, and a decision-support tool integrated into the electronic record were all enablers of success although patient psychosocial complexity remained a barrier to engagement in treatment., Conclusion: A multifaceted primary care improvement initiative increased clinician confidence and was associated with an increase in the proportion of HCV RNA positive patients who initiated curative treatment., Competing Interests: Conflict of interest: Drs. Ann Stewart and Tara Kiran were co-PIs on the study grant from Gilead Sciences Canada, a company that produces medications to treat Hepatitis C. However, the study sponsors had no role in study design, data collection, analysis and interpretation of data, manuscript preparation, or the decision to submit for publication., (© Copyright by the American Board of Family Medicine.)

Objectives: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension., Study Design and Setting: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity., Results: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators"., Conclusion: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies., Competing Interests: Declaration of Competing Interest Although Luis Gabriel Cuervo is an official of the Pan American Health Organization, the views expressed in this publication are his sole responsibility and do not necessarily represent the decisions or policies of the Pan American Health Organization (PAHO/WHO)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyse the association between the mortality during the summer 2022 and either high temperatures or the COVID-19 wave with data from the Catalan Health Care System (7.8 million people)., Methods: We performed a retrospective study using publicly available data of meteorological variables, influenza-like illness (ILI) cases (including COVID-19) and deaths. The study comprises the summer months of the years 2021 and 2022. To compare the curves of mortality, ILI and temperature we calculated the z -score of each series. We assessed the observed lag between curves using the cross-correlation function. Finally, we calculated the correlation between the z -scores using the Pearson correlation coefficient ( R 2 )., Results: During the study period, 33,967 deaths were reported in Catalonia (16,416 in the summer of 2021 and 17,551 in the summer of 2022). In 2022, the observed lag and the correlation between the z -scores of temperature and all-cause deaths was 3 days and R 2 = 0.86, while between ILI and all-cause deaths was 22 days and R 2 = 0.21. This high correlation between temperature and deaths increased up to 0.91 when we excluded those deaths reported as COVID-19 deaths, while the correlation between ILI and non-COVID-19 deaths decreased to -0.19. No correlation was observed between non-COVID deaths and temperature or ILI cases in 2021., Conclusion: Our study suggests that the main cause of the increase in deaths during summer 2022 in Catalonia was the high temperatures and its duration. The contribution of the COVID-19 seems to be limited., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Coma, Pino, Mora, Fina, Perramon, Prats, Medina, Planella, Mompart, Mendioroz and Cabezas.)

Background: Parent and physician perceptions of plant milk are unclear. Aim: To explore parent and physician perceptions of plant milk for children and to gain a better understanding of why parents and physicians might choose plant milk for children. Methods: A mixed methods study was conducted using a questionnaire and interviews with parents and physicians participating in the TARGet Kids! cohort study. Questionnaire data were analyzed using descriptive statistics. Interview transcripts were analyzed using thematic analysis. Results: Parents reported a variety of reasons for choosing plant milk for their children including concerns around allergies, the environment, animal welfare, plant-based diet, health benefits, taste and hormones in cow's milk. Parents gave their children various types of plant milks and physicians provided various recommendations to parents of children not consuming cow's milk. Our study identified that 79% of parents and 51% of physicians were unaware that soy milk is the recommended cow's milk substitute for children. Additionally, 26% of parents did not know some plant milks are not fortified and can contain added sugar. Three main themes were identified from interviews about why parents and physicians may choose plant milk for children: (i) healthiness of plant milk; (ii) concerns about hormones; and (iii) environmental impacts. Conclusions: Parents and physicians choose the milk that they believe is healthiest for their child or patient. However, a lack of clarity on the effects of plant milk consumption on children's health resulted in conflicting views on whether plant milk or cow's milk is healthier for children.

Gastrointestinal (GI) Endoscopy is a basic competence for the management of gastrointestinal diseases. However, it should not be regarded as an independent training technique. Rather it is a part of a continuous and accredited process that requires clinical knowledge from the gastroenterologist to keep skills up-to-date in a constantly evolving medical subspecialty. Thus, the only official accredited way for training in GI endoscopy is through the Specialized Health Training program in the Management of the Digestive Diseases administered by the Spanish Ministry of Health.

Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR.  Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: • Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. • The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: • Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. • Routine and semi-professional sports activities seem safe environments to promote during this pandemic., (© 2023. The Author(s).)