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Background: Cutaneous melanoma is the most aggressive form of skin cancer, responsible for most skin cancer-related deaths. Recent advances in artificial intelligence, jointly with the availability of public dermoscopy image datasets, have allowed to assist dermatologists in melanoma identification. While image feature extraction holds potential for melanoma detection, it often leads to high-dimensional data. Furthermore, most image datasets present the class imbalance problem, where a few classes have numerous samples, whereas others are under-represented., Methods: In this paper, we propose to combine ensemble feature selection (FS) methods and data augmentation with the conditional tabular generative adversarial networks (CTGAN) to enhance melanoma identification in imbalanced datasets. We employed dermoscopy images from two public datasets, PH2 and Derm7pt, which contain melanoma and not-melanoma lesions. To capture intrinsic information from skin lesions, we conduct two feature extraction (FE) approaches, including handcrafted and embedding features. For the former, color, geometric and first-, second-, and higher-order texture features were extracted, whereas for the latter, embeddings were obtained using ResNet-based models. To alleviate the high-dimensionality in the FE, ensemble FS with filter methods were used and evaluated. For data augmentation, we conducted a progressive analysis of the imbalance ratio (IR), related to the amount of synthetic samples created, and evaluated the impact on the predictive results. To gain interpretability on predictive models, we used SHAP, bootstrap resampling statistical tests and UMAP visualizations., Results: The combination of ensemble FS, CTGAN, and linear models achieved the best predictive results, achieving AUCROC values of 87% (with support vector machine and IR=0.9) and 76% (with LASSO and IR=1.0) for the PH2 and Derm7pt, respectively. We also identified that melanoma lesions were mainly characterized by features related to color, while not-melanoma lesions were characterized by texture features., Conclusions: Our results demonstrate the effectiveness of ensemble FS and synthetic data in the development of models that accurately identify melanoma. This research advances skin lesion analysis, contributing to both melanoma detection and the interpretation of main features for its identification., (© 2024. The Author(s).)

Background: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC., Methods: HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches., Results: HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment., Conclusions: These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction., (© 2024. The Author(s).)

Background: This systematic literature review aims to summarize global research on parental acceptance, attitudes, and knowledge regarding human papillomavirus vaccinations., Methods: The literature search was conducted in PubMed, Web of Science and Scopus, and included publications from 2006 to 2023. Study quality was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Meta-analyses were performed using random-effects models to estimate pooled parental acceptance of HPV vaccinations. Studies were stratified by study years, and a subgroup analysis was conducted to estimate vaccine acceptance rates by world regions. Additionally, sensitivity analyses examined the role of parents in accepting HPV vaccinations for children of different sexes., Results: Based on 86 studies, we found that parents generally supported HPV vaccinations for their children, yet HPV vaccine acceptance rates showed high variation (12.0 to 97.5%). The subgroup analysis revealed geographical variations in pooled parental HPV vaccine acceptance rates, with the highest rate observed in Africa (79.6%; 95% CI: 73.5-85.2; I² = 98.3%; p < 0.01) and the lowest in North America (56.7%; 95% CI: 49.3-64.0; I² = 99.4%; p < 0.01). Sensitivity analyses showed that acceptance was higher for daughters than for sons, with mothers more willing to get their daughters vaccinated. The proportion of parents reporting barriers or benefits regarding HPV vaccinations varied widely (0.3-95.8%) between study regions. Across all world regions, fear of adverse effects and concerns about vaccine safety were the main barriers, whereas the desire to protect their children from cancer was a significant predictor of vaccine acceptance. Knowledge levels varied widely (6.5 to 100%) between world regions and according to the questions asked. In most studies, knowledge e.g., that HPV is sexually transmitted, and that HPV vaccination provides protection against cervical cancer, ranged from moderate to high., Conclusions: The results indicated moderate parental acceptance of HPV vaccines. Public knowledge of HPV infection should be promoted, and special efforts should be made to minimize the existing barriers and increase vaccination accessibility and uptake., (© 2024. The Author(s).)

Background: Anthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10-15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatment METHODS: The EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections., Results: During the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04-0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure., Conclusion: Empagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group., (© 2024. The Author(s).)

Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis and causes a persistent infection that can leave cattle with no symptoms. Many countries have been able to successfully eradicate BLV through improved detection and management methods. However, with the increasing novel molecular detection methods there have been few efforts to standardize these results at global scale. This study aimed to determine the interlaboratory accuracy and agreement of 11 molecular tests in detecting BLV. Each qPCR/ddPCR method varied by target gene, primer design, DNA input and chemistries. DNA samples were extracted from blood of BLV-seropositive cattle and lyophilized to grant a better preservation during shipping to all participants around the globe. Twenty nine out of 44 samples were correctly identified by the 11 labs and all methods exhibited a diagnostic sensitivity between 74 and 100%. Agreement amongst different assays was linked to BLV copy numbers present in samples and the characteristics of each assay (i.e., BLV target sequence). Finally, the mean correlation value for all assays was within the range of strong correlation. This study highlights the importance of continuous need for standardization and harmonization amongst assays and the different participants. The results underscore the need of an international calibrator to estimate the efficiency (standard curve) of the different assays and improve quantitation accuracy. Additionally, this will inform future participants about the variability associated with emerging chemistries, methods, and technologies used to study BLV. Altogether, by improving tests performance worldwide it will positively aid in the eradication efforts., (© 2024. The Author(s).)

Objective: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD)., Methods: Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants., Results: Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases., Conclusion: Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients., (© 2024. The Author(s).)

Background: Healthcare professionals traditional education reflects constraints to face the complex needs of people with chronic diseases in primary care settings. Since more innovative and practical solutions are required, Virtual Community of Practices (vCoP) seem to better respond to learning updates, improving professional and organizational knowledge. However, little is known about the value created in vCoPs as social learning environments. The objective of this project was to explore the value creation process of a gamified vCoP ("e-mpodera vCoP") aimed at improving the knowledge and attitudes of primary healthcare professionals (PCPs) (nurses and general practitioners) to the empowerment of people with chronic conditions., Methods: A framework analysis assessed the value creation process using a mixed methods approach. The framework provided awareness about knowledge and usefulness in a learning community through five cycles: (1) immediate value, (2) potential value, (3) applied value, (4) realized value, and (5) reframing value. Quantitative data included vCoP analytics such as logins, contributions, points, badges, and performance metrics. Qualitative data consisted of PCPs' forum contributions from Madrid, Catalonia, and Canary Islands over 14 months., Results: A total of 185 PCPs had access to the e-mpodera vCoPs. The vCoP showed the dynamic participation of 146 PCPs, along 63 content activities posted, including a total of 3,571 contributions (including text, images, links to webpages, and other files). Regarding the value creation process, the e-mpodera vCoP seems to encompass a broad spectrum of value cycles, with indicators mostly related to cycle 1 (immediate value - activities and interactions) and cycle 2 (potential value - knowledge capital); and to a lesser extent for cycle 3 (applied value - changes in practice) and for cycle 4 (realized value - performance improvement). The presence of indicators related to cycle 5 (reframing value), was minimal, due to few individual redefinitions of success., Conclusion: To reach a wider range of value possibilities, a combination of learning objectives, competence framework, challenged-based gamified platform, and pathway model of skill development seems crucial. However, additional research is required to gain clearer insights into organizational values, professionals' lifelong educational needs in healthcare, and the long-term sustainability of performance improvement., Trial Registration: ClinicalTrials.gov, NCT02757781. Registered on 02/05/2016., (© 2024. The Author(s).)

Background: Intravesical Bacillus Calmette-Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach., Case Presentation: We present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus., Conclusion: Granulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique., (© 2024. The Author(s).)

Background: The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment., Methods and Results: A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1's efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways., Conclusion: The study's results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks., (© 2023. The Author(s).)

Gay, bisexual, and other men who have sex with men (GBMSM) experience a high prevalence of psychosocial health problems, such as harmful substance use and depression, as well as being disproportionately affected by HIV. HIV Pre-Exposure Prophylaxis (PrEP) may provide psychosocial benefits beyond its intended purpose of reducing HIV infection. We explore the psychosocial impact of oral PrEP use on gay men in England using qualitative data from the PROUD study. From February 2014 to January 2016, semi-structured in-depth interviews were conducted with 40 gay men and one trans woman. Participants were purposively recruited based on trial arm allocation, adherence, and sexual risk behaviours. By removing HIV risk from sex, PrEP improves users' wellbeing by reducing HIV-related anxiety and internalised stigma and increasing HIV prevention self-efficacy, sexual pleasure, and intimacy. In turn, these psychological changes may influence behaviour in the form of greater sexual freedom, reduced harmful drug use, and more protective sexual health behaviours. However, PrEP may create internal conflict for some gay men, due to its disruption of social norms around condom use and its perceived influence on their sexual behaviour leading to reduced condom self-efficacy. These findings provide a baseline of PrEP's psychosocial impact amongst some of the first PrEP users in England and supports calls to consider the psychosocial impact of PrEP in prescribing guidelines., (© 2023. The Author(s).)

Intellectual disability (ID) has a prevalence of 1-3% and aproximately 30-50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren't clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice., (© 2023. The Author(s).)

Background: Pornography consumption is higher in men, but we do not know if this association can be modified by different variables, such as sexual attraction and place of origin. Given the impact pornography has on minors, there are limited studies that analyze the use of pornography in representative samples of the adult population. The aim was analyze the prevalence and factors associated with using pornography in young adult men and women, living in Spain, with different sexual attractions and different places of birth., Methods: Cross-sectional study with an online survey conducted with 2515 men and women aged between 18 and 35 years of age. The prevalence of pornography consumption is described and analyzed in the total sample and stratified by sex, according to socio-demographic and sexual attraction variables. The association between covariates and pornography consumption at some point in life was estimated with prevalence ratios (PR) obtained with the Poisson models of robust variance., Dependent Variable: voluntarily using pornography at some point in life. Socio-demographic variables were included in the analysis: age, sex, level of education, place of birth. Sexual attraction was also analyzed., Results: In Spain, 94.7% of men between 18 and 34 years and 74.6% of women have voluntarily used pornography at some point in their life. The mean age to start using it is earlier in men [Mean:14.2; Standard Deviation (SD):2.3]. Bisexual/homosexual attraction (reference: heterosexual) increases the probability of using pornography in women [(PR (95%CI): 1.30 (1.22; 1.38)]. Yet this is not observed in men. In both sexes, the probability of using pornography increases with age [(PR (95%CI): 1.01(1.00; 1.01)] and coming from abroad (reference: native), being the effect of country of birth significantly higher in women [(PR (95%CI): 1.17 (1.09; 1.26)] than in men [(PR (95%CI): 1.04 (1.01; 1.07)., Conclusions: Public health programmes aimed at improving affective-sexual health should consider the high use of pornography among young adults in Spain, as well as those variables that increase its use., (© 2023. The Author(s).)

Background: Prevalence of musculoskeletal pain is high among eldercare workers, and therapeutic exercise has shown to be effective for its management. Although telerehabilitation is an increasingly used alternative for delivering therapeutic exercise, no studies have assessed synchronous group telerehabilitation interventions for the management of musculoskeletal disorders. Thus, the aim of this article is to describe the protocol of a randomized controlled trial that will assess the effects of a videoconference-based group therapeutic exercise intervention on the musculoskeletal pain of eldercare workers., Methods: This multicenter trial will randomly assign 130 eldercare workers to either a control or experimental group. Participants in the control group will not receive any intervention, and participants in the experimental group will take part in a 12-week remote supervised videoconference-based intervention, consisting of 2 weekly 45-min group sessions. Each session will include 4 sets of 6 progressive resistance exercises for the lower limbs, upper limbs and trunk, performed with bodyweight and elastic bands at moderate-high intensity. Following the 12 weeks, participants in the experimental group will be provided with material for autonomously carry on the therapeutic exercises and advised to continue performing 2 weekly sessions on their own until a 48-week follow-up. Assessments will be performed at baseline, 12 and 48 weeks. Primary outcome will be average pain intensity in the low back during the last 7 days, measured by the 0-10 Numerical Rating Scale. Secondary outcomes will include additional measures of musculoskeletal pain, psycho-affective state, work-related variables, and physical fitness., Discussion: This will be the first trial, to our knowledge, assessing whether a remote delivery of a group therapeutic exercise intervention via videoconference is effective for reducing the musculoskeletal pain, improving the psycho-affective state and physical fitness, and enhancing the work-related parameters in eldercare workers. If successful, this study will provide innovative tools for implementing effective, scalable and affordable interventions to tackle musculoskeletal disorders in the workplace. It will also highlight the utility of telehealth, and address the importance of therapeutic exercise to manage musculoskeletal pain in a critical population for the future of the aging societies as it is the eldercare workers., Trial Registration: The study protocol was prospectively registered at ClinicalTrials.gov (registration number: NCT05050526) on September 20, 2021., (© 2023. The Author(s).)

Background: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life., Methods: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies., Results: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%)., Conclusions: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice., (© 2023. The Author(s).)

Background: Chronic stress can produce a severe negative impact on health not only in the exposed individuals but also in their offspring. Indeed, chronic stress may be contributing to the current worldwide scenario of increasing infertility and decreasing gamete quality in human populations. Here, we evaluate the effect of chronic stress on behavior and male reproductive parameters in zebrafish. Our goal is to provide information on the impact that chronic stress has at molecular, histological, and physiological level in a vertebrate model species., Results: We evaluated the effects of a 21-day chronic stress protocol covering around three full waves of spermatogenesis in Danio rerio adult males. The induction of chronic stress produced anxiety-like behavior in stressed males as assessed by a novel tank test. At a molecular level, the induction of chronic stress consistently resulted in the overexpression of two genes related to endoplasmic reticulum (ER) stress in the brain. Gene set enrichment analysis (GSEA) of testes suggested a dysregulation of the nonsense-mediated decay (NMD) pathway, which was also confirmed on qPCR analysis. Histological analysis of the testicle did not show significant differences in terms of the relative proportions of each germ-cell type; however, the quality of sperm from stressed males was compromised in terms of motility. RNA-seq analysis in stress-derived larval progenies revealed molecular alterations, including those predicted to affect translation initiation, DNA repair, cell cycle control, and response to stress., Conclusions: Induction of chronic stress during a few cycles of spermatogenesis in the vertebrate zebrafish model affects behavior, gonadal gene expression, final gamete quality, and progeny. The NMD surveillance pathway (a key cellular mechanism that regulates the stability of both normal and mutant transcripts) is severely affected in the testes by chronic stress and therefore the control and regulation of RNAs during spermatogenesis may be affected altering the molecular status in the progeny., (© 2023. The Author(s).)

Background: Older people achieve lower levels of antibody titers than younger populations after Covid-19 vaccination and show a marked waning humoral immunity over time, likely due to the senescence of the immune system. Nevertheless, age-related predictive factors of the waning humoral immune response to the vaccine have been scarcely explored. In a cohort of residents and healthcare workers from a nursing home that had received two doses of the BNT162b2 vaccine, we measured specific anti-S antibodies one (T1), four (T4), and eight (T8) months after receiving the second dose. Thymic-related functional markers, including thymic output, relative telomere length, and plasma thymosin-α1 levels, as well as immune cellular subsets, and biochemical and inflammatory biomarkers, were determined at T1, and tested for their associations with the magnitude of the vaccine response (T1) and the durability of such response both, at the short- (T1-T4) and the long-term (T1-T8). We aimed to identify age-related factors potentially associated with the magnitude and persistence of specific anti-S immunoglobulin G (IgG)-antibodies after COVID-19 vaccination in older people., Results: Participants (100% men, n = 98), were subdivided into three groups: young (< 50 years-old), middle-age (50-65 years-old), and older (≥65 years-old). Older participants achieved lower antibody titers at T1 and experienced higher decreases in both the short- and long-term. In the entire cohort, while the magnitude of the initial response was mainly associated with the levels of homocysteine [β (95% CI); - 0.155 (- 0.241 to - 0.068); p = 0.001], the durability of such response at both, the short-term and the long-term were predicted by the levels of thymosin-α1 [- 0.168 (- 0.305 to - 0.031); p = 0.017, and - 0.123 (- 0.212 to - 0.034); p = 0.008, respectively]., Conclusions: Higher plasma levels of thymosin-α1 were associated with a lower waning of anti-S IgG antibodies along the time. Our results suggest that plasma levels of thymosin-α1 could be used as a biomarker for predicting the durability of the responses after COVID-19 vaccination, possibly allowing to personalize the administration of vaccine boosters., (© 2023. The Author(s).)

Background: Although the human papillomavirus (HPV) vaccine has been recommended in Germany for girls since 2007, no organised vaccination programme was introduced and HPV vaccine coverage remains low. We investigated the HPV vaccination rates from 2008 to 2018 and the effects of HPV vaccination on anogenital warts and precancerous lesions in young women in Bavaria, Germany, a state with low vaccination rates., Methods: Retrospective analyses of claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) on females born between 1990 and 2009 (9 to 28 years old in 2018) were conducted to calculate vaccination rates by birth cohort, proportion of vaccine types administered and incidence of anogenital warts and precancerous lesions of the cervix uteri. 942 841 Bavarian females 9 to 28 years old with available information on HPV vaccination were included to calculate vaccination rates. For the outcome analyses, data from 433 346 females 19 to 28 years old were analysed. Hazard ratios (HR) were computed from univariable and multivariable Cox regression models comparing vaccinated and unvaccinated women, considering type of vaccine used and contraceptive prescription., Results: 40·9% of 18-year-olds and only 13·3% of 12-year-olds were fully vaccinated in 2018 in Bavaria. Gardasil® and Gardasil9® were most commonly administered. Vaccinated compared to unvaccinated women had a lower incidence of anogenital warts and cervical lesions, however only small differences were detected between fully and partially vaccinated women. Fully vaccinated women had a 63% (HR 0·37 (95% confidence interval (CI) 0·34 to 0·40) and 23% (HR 0·77, 95%CI 0·71 to 0·84) lower risk of anogenital warts and cervical lesions, respectively. Women who were prescribed contraceptives prior to vaccination had a 49% higher risk of developing anogenital warts (HR 1·49, 95%CI 1·25 to 1·79) or cervical lesions (HR 1·49, 95%CI 1·27 to 1·75) compared to vaccinated women without contraceptive prescription., Conclusions: The evaluation of the effects of HPV vaccination in Bavaria showed a promising decline of anogenital warts and precancerous lesions in vaccinated young women. However, an increase in vaccination rates is necessary to achieve a greater population impact in preventing HPV-related diseases., (© 2022. The Author(s).)

Background: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival., Methods: PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established., Results: Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m 2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009]., Conclusion: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis., (© 2022. The Author(s).)

Background: Controversy exists regarding the relationship of the outcome of patients with colorectal cancer (CRC) with the time from symptom onset to diagnosis. The aim of this study is to investigate this association, with the assumption that this relationship was nonlinear and with adjustment for multiple confounders, such as tumor grade, symptoms, or admission to an emergency department., Methods: This multicenter study with prospective follow-up was performed in five regions of Spain from 2010 to 2012. Symptomatic cases of incident CRC from a previous study were examined. At the time of diagnosis, each patient was interviewed, and the associated hospital and clinical records were reviewed. During follow-up, the clinical records were reviewed again to assess survival. Cox survival analysis with a restricted cubic spline was used to model overall and CRC-specific survival, with adjustment for variables related to the patient, health service, and tumor., Results: A total of 795 patients had symptomatic CRC and 769 of them had complete data on diagnostic delay and survival. Univariate analysis indicated a lower HR for death in patients who had diagnostic intervals less than 4.2 months. However, after adjustment for variables related to the patient, tumor, and utilized health service, there was no relationship of the diagnostic delay with survival of patients with colon and rectal cancer, colon cancer alone, or rectal cancer alone. Cubic spline analysis indicated an inverse association of the diagnostic delay with 5-year survival. However, this association was not statistically significant., Conclusions: Our results indicated that the duration of diagnostic delay had no significant effect on the outcome of patients with CRC. We suggest that the most important determinant of the duration of diagnostic delay is the biological profile of the tumor. However, it remains the responsibility of community health centers and authorities to minimize diagnostic delays in patients with CRC and to implement initiatives that improve early diagnosis and provide better outcomes., (© 2022. The Author(s).)

Background: Alport syndrome is a hereditary kidney disease characterized by hematuria and proteinuria. Although there have been reports of autosomal dominant COL4A4 variants, this is likely an underdiagnosed condition. Improved access to affordable genetic testing has increased the diagnosis of Alport syndrome. As genetic testing becomes ubiquitous, it is imperative that clinical nephrologists understand the benefits and challenges associated with clinical genetic testing., Case Presentation: We present a family of Mexican descent with a heterozygous COL4A4 variant (c.5007delC, ClinVar accession numbers: SCV001580980.2, SCV001993731.1) not previously discussed in detail in the literature. The proband received a biopsy diagnosis suggestive of Fabry disease 18 years after she first developed hematuria and progressed to chronic kidney disease stage III. One year later, the proband was provisionally diagnosed with Alport syndrome after a variant of uncertain significance in the COL4A4 gene was identified following targeted family variant testing of her daughter. Upon review of the medical histories of the proband's children and niece, all but one had the same variant. Of the four with the variant, three display clinical symptoms of hematuria, and/or proteinuria. The youngest of the four, only months old, has yet to exhibit clinical symptoms. Despite these findings there was a considerable delay in synthesizing this data, as patients were tested in different commercial genetic testing laboratories. Subsequently, understanding this family's inheritance pattern, family history, and clinical symptoms, as well as the location of the COL4A4 variant resulted in the upgrade of the variant's classification. Although the classification of this variant varied among different clinical genetic testing laboratories, the consensus was that this variant is likely pathogenic., Conclusions: This COL4A4 variant (c.5007delC) not yet discussed in detail in the literature is associated with Alport syndrome. The inheritance pattern is suggestive of autosomal dominant inheritance. This report highlights the intricacies of variant interpretation and classification, the siloed nature of commercial genetic testing laboratories, and the importance of a thorough family history for proper variant interpretation. Additionally, the cases demonstrate the varied clinical presentations of Alport syndrome and suggest the utility of early screening, diagnosis, monitoring, and treatment., (© 2022. The Author(s).)

Background: Recovery of hand function is crucial for the independence of people with spinal cord injury (SCI). Wearable devices based on soft robotics (SR) or functional electrical stimulation (FES) have been employed to assist the recovery of hand function both during activities of daily living (ADLs) and during therapy. However, the implementation of these wearable devices has not been compiled in a review focusing on the functional outcomes they can activate/elicit/stimulate/potentiate. This narrative review aims at providing a guide both for engineers to help in the development of new technologies and for clinicians to serve as clinical guidelines based on the available technology in order to assist and/or recover hand function in people with SCI., Methods: A literature search was performed in Scopus, Pubmed and IEEE Xplore for articles involving SR devices or FES systems designed for hand therapy or assistance, published since 2010. Only studies that reported functional outcomes from individuals with SCI were selected. The final collections of both groups (SR and FES) were analysed based on the technical aspects and reported functional outcomes., Results: A total of 37 out of 1101 articles were selected, 12 regarding SR and 25 involving FES devices. Most studies were limited to research prototypes, designed either for assistance or therapy. From an engineering perspective, technological improvements for home-based use such as portability, donning/doffing and the time spent with calibration were identified. From the clinician point of view, the most suitable technical features (e.g., user intent detection) and assessment tools should be determined according to the particular patient condition. A wide range of functional assessment tests were adopted, moreover, most studies used non-standardized tests., Conclusion: SR and FES wearable devices are promising technologies to support hand function recovery in subjects with SCI. Technical improvements in aspects such as the user intent detection, portability or calibration as well as consistent assessment of functional outcomes were the main identified limitations. These limitations seem to be be preventing the translation into clinical practice of these technological devices created in the laboratory., (© 2022. The Author(s).)

Background: Generalized anxiety disorder (GAD) is one of the most prevalent mental health problems. Patients with GAD have unmet needs related to the information received about their disorder, its treatments and their participation in the decision-making process. The aim of this study is to develop and assess the acceptability of a patient decision aid (PtDA) for patients with GAD., Method: The PtDA was developed following the International Patient Decision Aid Standards. The recommendations of the Spanish clinical practice guideline (CPG) for patients with GAD were used as the basis. The first prototype was developed by an expert committee, further improvements were made with patients (n = 2), clinical experts (n = 13) and the project management group (n = 7). The acceptability of this second draft was assessed by patients non-involved in the previous phases (n = 11)., Results: The final PtDA version included a brief description of GAD and its treatments. Most participants agreed that the PtDA was easy to use, visually appealing and useful. At least half of the participants learned new things about treatments and adverse effects., Conclusions: A PtDA was developed for patients with GAD based on recommendations from the Spanish CPG. It was improved and accepted by patients and clinical experts involved. An evaluation of its effectiveness on the shared decision-making process during the clinical encounter is planned., (© 2022. The Author(s).)

Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it's clinical, serological and histologic characteristics., Materials and Methods: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up., Results: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1-5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8-12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not., Conclusions: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients., (© 2022. The Author(s).)

Background: Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA., Methods: Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis., Results: Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213-376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7-4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. -174 [95% CI -213 to -135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment., Conclusion: The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients., (© 2022. The Author(s).)

Background: Machismo and acceptance of violence (AV) against women are part of the social construction of hegemonic masculinity and are related to the risk of dating violence. This study aims to analyze the effectiveness of the Lights4Violence program in reducing machismo and AV in secondary school students from different European cities., Methods: Quasi-experimental longitudinal study using a convenience sample of 1,146 high school students from different European cities (12-17 years old) including 575 intervention group students (59.1% girls) and 571 control group students (62.7% girls). We performed linear regression models to identify the effect of the intervention, modelling the difference in means in machismo and AV (dependent variables) between wave-2 and wave-1., Results: An interaction was identified between the group variable and the empathy variable. In wave-2, girls with high empathy at baseline in the intervention group obtained lower mean AV scores (β: -0.131; p = 0.004). However, the boys in the intervention group (reference: control group) with low empathy at baseline registered a significant increase in the mean values of machismo (β: 0.247; p < 0.001)., Conclusion: The importance of empathy is shown in the effectiveness of interventions to reduce machismo and AV in adolescents. While the Lights4Violence program focuses on promoting healthy relationships, there were some controversial results. It is possible that some children, especially those with less empathy, may have felt "challenged" during the intervention and/or assessment. This suggests the need for the development of interventions that also consider psychological processes and integrate the promotion of positive expressions of masculinity., (© 2022. The Author(s).)

Background: The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) are self-report measures of major depressive disorder and generalised anxiety disorder. The primary aim of this study was to test for differential item functioning (DIF) on the PHQ-9 and GAD-7 items based on age, sex (males and females), and country., Method: Data from nationally representative surveys in UK, Ireland, Spain, and Italy (combined N = 6,054) were used to fit confirmatory factor analytic and multiple-indictor multiple-causes models., Results: Spain and Italy had higher latent variable means than the UK and Ireland for both anxiety and depression, but there was no evidence for differential items functioning., Conclusions: The PHQ-9 and GAD-7 scores were found to be unidimensional, reliable, and largely free of DIF in data from four large nationally representative samples of the general population in the UK, Ireland, Italy and Spain., (© 2022. The Author(s).)

Background: Given the potential benefits of introducing ultrasound in the clinical assessment of muscle disorders, this study aimed to assess the feasibility and reliability of measuring forearm muscle thickness by ultrasound in a geriatric clinical setting., Methods: Cross-sectional pilot study in 25 participants (12 patients aged ≥ 70 years in an acute geriatric ward and 13 healthy volunteers aged 25-50 years), assessed by three raters. Muscle thickness measurement was estimated as the distance between the subcutaneous adipose tissue-muscle interface and muscle-bone interface of the radius at 30% proximal of the distance between the styloid process and distal insertion of the biceps brachii muscle of the dominant forearm. Examinations were repeated three times by each rater and intra- and inter-rater reliability was calculated. Feasibility analysis included consideration of technological, economic, legal, operational, and scheduling (TELOS) components., Results: Mean muscle-thickness measurement difference between groups was 4.4 mm (95% confidence interval [CI] 2.4 mm to 6.3 mm], p < 0.001). Intra-rater reliability of muscle-thickness assessment was excellent, with intraclass correlation coefficient (ICC) of 0.947 (95%CI 0.902 to 0.974), 0.969 (95%CI 0.942 to 0.985), and 0.950 (95%CI 0.907 to 0.975) for observer A, B, and C, respectively. Inter-rater comparison showed good agreement (ICC of 0.873 [95%CI 0.73 to 0.94]). Four of the 17 TELOS components considered led to specific recommendations to improve the procedure's feasibility in clinical practice., Conclusion: Our findings suggest that US is a feasible tool to assess the thickness of the forearm muscles with good inter-rater and excellent intra-rater reliability in a sample of hospitalized geriatric patients, making it a promising option for use in clinical practice., (© 2022. The Author(s).)

Background: Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8 + T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4 + and CD8 + subpopulations, and changes in markers of cellular ageing in CD8 + T lymphocytes., Methods: Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8 + and CD4 + lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8 + T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16 INK4a and p21 CIP1/Waf1 ., Results: The number of CD8 + TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16 INK4a in CD8 + lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8 + lymphocytes in healthy controls, but this shift was less apparent in PD patients., Conclusions: Taken together, our data demonstrate a reduction in CD8 + T cell replicative senescence which is present at the earliest stages of Parkinson's disease., (© 2021. The Author(s).)

Background: Increased systemic and tissue levels of interleukin (IL)-1β are associated with greater risk of impaired neurodevelopment after birth. In this study, we tested the hypothesis that systemic IL-1 receptor antagonist (Ra) administration would attenuate brain inflammation and injury in near-term fetal sheep exposed to lipopolysaccharide (LPS)., Methods: Chronically instrumented near-term fetal sheep at 0.85 of gestation were randomly assigned to saline infusion (control, n = 9), repeated LPS infusions (0 h = 300 ng, 24 h = 600 ng, 48 h = 1200 ng, n = 8) or repeated LPS plus IL-1Ra infusions (13 mg/kg infused over 4 h) started 1 h after each LPS infusion (n = 9). Sheep were euthanized 4 days after starting infusions for histology., Results: LPS infusions increased circulating cytokines and were associated with electroencephalogram (EEG) suppression with transiently reduced mean arterial blood pressure, and increased carotid artery perfusion and fetal heart rate (P < 0.05 vs. control for all). In the periventricular and intragyral white matter, LPS-exposure increased IL-1β immunoreactivity, numbers of caspase 3+ cells and microglia, reduced astrocyte and olig-2+ oligodendrocyte survival but did not change numbers of mature CC1+ oligodendrocytes, myelin expression or numbers of neurons in the cortex and subcortical regions. IL-1Ra infusions reduced circulating cytokines and improved recovery of EEG activity and carotid artery perfusion. Histologically, IL-1Ra reduced microgliosis, IL-1β expression and caspase-3+ cells, and improved olig-2+ oligodendrocyte survival., Conclusion: IL-1Ra improved EEG activity and markedly attenuated systemic inflammation, microgliosis and oligodendrocyte loss following LPS exposure in near-term fetal sheep. Further studies examining the long-term effects on brain maturation are now needed., (© 2021. The Author(s).)

Background: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data., Results: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/μL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve., Conclusion: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

Background: Possible cases of SARS-CoV-2 infection were diagnosed in primary care in Madrid, some of these cases had pneumonia. Most of the SARS-CoV-2 pneumonia published data came from hospitalised patients. This study set out to describe clinical characteristics of patients with SARS-CoV-2 pneumonia diagnosed in primary care across age groups and type of pneumonia., Methods: Observational retrospective study obtaining clinical data from the electronic health records of patients who were followed-up by SARS-CoV-2 possible infection in a primary care practice in Madrid. All the cases were collected by in-person or remote consultation during the 10th March to the 7th of April., Exposure: Diagnosis of SARS-CoV-2 pneumonia by chest X-ray ordered by the GP. Main outcomes and measures: Symptoms of SARS-CoV-2 pneumonia, physical examination and diagnostic tests as a blood test, nasopharyngeal swab results for RT-PCR (Reverse transcriptase-polymerase chain reaction) and chest X-ray results., Results: The overall SARS-CoV-2 pneumonias collected were 172 (female 87 [50.6%], mean age 60.5 years standard deviation [SD] 17.0). Comorbidities were body mass index ≥ 25 kg/m 2 (90 [52.3%]), hypertension (83 [48.3%]), dyslipidaemia (68 [39.5%]) and diabetes (33 [19.2%]). The sample was stratified by age groups (< 50 years, 50-75 years and ≥ 75 years). Clinical manifestations at onset were fever (144 [83.7%]), cough (140 [81.4%]), dyspnoea (103 [59.9%]) and gastrointestinal disturbances (72 [41.9%]). Day 7.8 (SD:4.1) from clinical onset was the mean day of pneumonia diagnosis. Bilateral pneumonia was more prevalent than unilateral (126 [73.3%] and 46 [26.7%]). Patients with unilateral pneumonia were prone to higher pulse oximetry (96% vs 94%, p < 0.001). We found differences between unilateral and bilateral cases in C-reactive protein (29.6 vs 81.5 mg/L, p < 0.001), and lymphocytes (1400.0 vs 1000.0E3/ml, p < 0.001). Complications were registered: 42 (100%) of patients ≥ 75 years were admitted into hospital; pulmonary embolism was only present at bilateral pneumonia (7 patients [5.6%]) and death occurred in 1 patient with unilateral pneumonia (2.2%) vs 10 patients (7.9%) with bilateral pneumonia ( p 0.170)., Conclusion: Clinical manifestations of SARS-CoV-2 pneumonia were fever, cough and dyspnoea; this was especially clear in the elderly. We described different characteristics between unilateral and bilateral pneumonia.

Background: Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA., Methods: This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1., Results: Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level., Conclusions: Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.

Background: Acute intermittent porphyria (AIP) is a genetic disease characterized by acute neurovisceral attacks. Long-term clinical conditions, chronic symptoms and impaired health related quality of life (HRQoL) have been reported during non-attack periods but mainly in patients with recurrent attacks. Our aim was to investigate these aspects in sporadic AIP (SA-AIP) and latent AIP (L-AIP) patients. Fifty-five participants, 27 SA-AIP (< 4 attacks/year) and 28 L-AIP patients with a prevalent founder mutation from Spain were included. Medical records were reviewed, and individual interviews, physical examinations, biochemical analyses, and abdominal ultrasound scans were conducted. HRQoL was assessed through an EQ-5D-5L questionnaire. A comparative study was made between SA-AIP and L-AIP patients., Results: The earliest long-term clinical condition associated with SA-AIP was chronic kidney disease. Chronic symptoms were reported in 85.2 % of SA-AIP and 46.4 % of L-AIP patients. Unspecific abdominal pain, fatigue, muscle pain and insomnia were significantly more frequent in SA-AIP than in L-AIP patients. The EQ-5D-5L index was lower in SA-AIP (0.809 vs. 0.926, p = 0.0497), and the impact of "pain", "anxiety-depression" and "mobility" was more intense in the EQ-5D-5L domains in SA-AIP than in L-AIP subjects and the general Spanish population., Conclusions: AIP remains a chronically symptomatic disease that adversely affects health and quality of life, even in patients with low rate of acute attacks. We suggest a regular monitoring of patients with symptomatic AIP regardless of their attack rate or the time since their last attack, with proper pain management and careful attention to kidney function.

Objective: It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients with respect to controls and whether these changes were associated with disease-related data., Methods: Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences., Results: The multivariable analysis adjusted for demographic characteristics, cardiovascular risk factors, and lipid-related molecules showed that total cholesterol (beta coefficient: - 22 [95%CI - 37 to - 7], p = 0.004), triglycerides (beta coefficient: 24 [95%CI 2-47], p = 0.033), lipoprotein A (beta coefficient: 22 [95%CI 2-43], p = 0.033), and CEC (beta coefficient: - 6 [95%CI - 10 to - 2]%,p = 0.002) were significantly different between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: - 0.21 [95%CI - 0.37 to - 0.05]%, p = 0.011) after multivariable adjustment., Conclusion: SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.

Background: Generalized anxiety disorder (GAD) is one of the most common mental disorders in primary care (PC). GAD has low remission and high relapse rates over long follow-up periods. Qualitative evidence was synthesized to understand the implementation of care and treatment options for people with GAD in PC., Methods: Research published from 2008 to September 2020 was searched in five databases (MEDLINE, EMBASE, CINAHL, WOS and PsycArticles). Studies that used qualitative methods for data collection and analysis to investigate the implementation of care and treatment options for people with GAD in PC and outpatient settings were included. Non-qualitative studies, mixed methods studies that did not separately report qualitative findings and studies in languages other than English or Spanish were excluded. We used the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) framework to assess the overall confidence in the findings., Results: The results with a moderate level of confidence showed that the trajectory of care for people with GAD in PC and outpatient settings is long and fluctuates over time, involving multiple difficulties in accessing and maintaining initial treatment or successive treatment options. In addition, there are wide variations in the preferences for and acceptability of different treatment options. The results with a high level of confidence indicated that more information on GAD and its treatment options is needed for PC practitioners, GAD patients and their carers. The results with a low level of confidence suggested that patients use antidepressants for longer than recommended and that the interruption of treatment is not usually planned., Conclusions: Initial resistance to new treatments among people with GAD can make access and adherence to treatment difficult. Improving care may require patients to be informed of possible trajectories in stepped care pathways before the initiation of treatment so they are aware that they may need to try a number of options until the most effective treatment for them is found. Increased awareness of and information materials on GAD may facilitate both appropriate diagnosis and long-term care.

Background: Improved colorectal cancer (CRC) survival rates have been reported over the last years, with more than half of these patients surviving more than 5 years after the initial diagnosis. Better understanding these so-called long-term survivors could be very useful to further improve their prognosis as well as to detect other problems that may cause a significant deterioration in their health-related quality of life (HRQoL). Cure models provide novel statistical tools to better estimate the long-term survival rate for cancer and to identify characteristics that are differentially associated with a short or long-term prognosis. The aim of this study will be to investigate the long-term prognosis of CRC patients, characterise long-term CRC survivors and their HRQoL, and demonstrate the utility of statistical cure models to analyse survival and other associated factors in these patients., Methods: This is a single-centre, ambispective, observational follow-up study in a cohort of n = 1945 patients with CRC diagnosed between 2006 and 2013. A HRQoL sub-study will be performed in the survivors of a subset of n = 485 CRC patients for which baseline HRQoL data from the time of their diagnosis is already available. Information obtained from interviews and the clinical records for each patient in the cohort is already available in a computerised database from previous studies. This data includes sociodemographic characteristics, family history of cancer, comorbidities, perceived symptoms, tumour characteristics at diagnosis, type of treatment, and diagnosis and treatment delay intervals. For the follow-up, information regarding local recurrences, development of metastases, new tumours, and mortality will be updated using hospital records. The HRQoL for long-term survivors will be assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. An analysis of global and specific survival (competitive risk models) will be performed. Relative survival will be estimated and mixture cure models will be applied. Finally, HRQoL will be analysed through multivariate regression models., Discussion: We expect the results from this study to help us to more accurately determine the long-term survival of CRC, identify the needs and clinical situation of long-term CRC survivors, and could be used to propose new models of care for the follow-up of CRC patients.

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. Standard therapy for heart failure (HF) is recommended for CTRCD, but there is no well-established evidence on how sacubitril/valsartan may help cancer patients with cardiotoxicity., Objectives: The aim of this trial was to study the effectiveness of sacubitril-valsartan in patients with CTRCD treated in cardio-oncology units., Methods: We enrolled 635 patients with breast cancer and followed them with echocardiography and NT- proBNP. Patients who developed left ventricular dysfunction and heart failure were treated with angiotensin-converting enzyme inhibitors (ACEI) (enalapril) or angiotensin receptor blockers (ARB) (valsartan), aldosterone antagonists (eplerenone), digitalis and diuretics (furosemide), as needed. When patients remained symptomatic and met the PARADIGM-HF inclusion criteria, sacubitril/valsartan was started instead of enalapril or valsartan. We analyzed clinical, laboratory and echocardiographic variables to determine the beneficial effects of sacubitril/valsartan on left ventricular remodeling (improvement of left ventricular ejection fraction (LVEF), left ventricle internal diameter in diastole), diastolic dysfunction (E/e' ratio), reduction in NT-proBNP levels, New York Heart Association (NHYA) class and improvement in the 6-min walk test. Also, we analyzed serum creatinine and potassium levels to determine treatmentsafety in this population. Median follow-up was 20 months., Results: Twenty-eight patients developed cardiotoxicity and were treated with sacubitril/valsartan. The sacubitril/valsartan dose was 100 mg (sacubitril 49 mg/valsartan 51 mg) in 12 patients (42.85%) and 200 mg (sacubitril 97 mg/valsartan 103 mg) in 16 patients (57.15%). No deaths were reported, and one patient underwent heart transplantation. Baseline median NT-proBNP was 997.5 pg/ml (IQR 663.8 - 2380.8), which decreased to a median of 416.5 pg/ml (IQR 192.0-798.2) on follow-up with p < 0.001. Baseline NYHA functional class was III (78.6%) or IV (21.4%), and it improved to I (57.1%) or II (42.9%) on follow-up. LVEF increased with treatment from 26.7 ± 5.4% to 32.3 ± 5.5% (p < 0.001). There were also significant improvements in left ventricle internal diameter in diastole (LVIDD), diastolic function, 6-min walk test, and mitral valve regurgitation. There were no differences between basal and follow-up levels of serum creatinine or potassium., Conclusion: Sacubitril/valsartan might be a promising treatment option in patients with refractory CTRCD.

Background: Osteoarthritis (OA) is a health condition sensitive to patient's preferences and values regarding the benefits and risks of the different treatment options. In this sense, patient decision aids (PtDA) can play an important role in helping patients to incorporate their values, needs, and preferences into the decision-making process, thus improving person-centered care. Previous research has focused almost exclusively on knee OA, and therefore, the aim of this study is to develop and evaluate the effectiveness of a PtDA for patients with hip OA., Methods: The general design consists of two phases: (1) design a web-based PtDA for patients with hip OA, following the recommended procedures: systematic review of safety/effectiveness of treatments, and an iterative process of development with the help of an Advisory Committee composed of health professionals and patients, and (2) to evaluate the impact of the PtDA on hip OA patients' decision-making process related with their treatment. For that aim, a multicenter randomized controlled trial will be carried out with 124 patients with hip OA in Tenerife (Spain) comparing intervention or usual care., Discussion: PtDAs have been recommended as a useful and effective resource for improving PCC in many health conditions. The intervention is intended to empower patients by fostering their active participation during the decision-making process about their treatment and by ensuring they make informed decisions congruent with their values and preferences. This study will contribute to the scientific knowledge about effectiveness of PtDAs in hip OA, in order to improve the quality of health care offered to these patients., Trial Registration: ClinicalTrials.gov NCT04241978 . Registered on 24 January 2020.

Background: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor., Results: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course., Conclusions: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease., Competing Interests: Competing interestsThe authors stated no conflicts of interest., (© The Author(s) 2020.)

Background: Mutations in CRYAA, which encodes the α-crystallin protein, are associated with a spectrum of congenital cataract-microcornea syndromes., Results: In this study, we performed clinical examination and subsequent genetic analysis in two unrelated sporadic cases of different geographical origins presenting with a complex phenotype of ocular malformation. Both cases manifested bilateral microphthalmia and severe anterior segment dysgenesis, primarily characterized by congenital aphakia, microcornea, and iris hypoplasia/aniridia. NGS-based analysis revealed two novel single nucleotide variants occurring de novo and affecting the translation termination codon of the CRYAA gene, c.520T > C and c.521A > C. Both variants are predicted to elongate the C-terminal protein domain by one-third of the original length., Conclusions: Our report not only expands the mutational spectrum of CRYAA but also identifies the genetic cause of the unusual ocular phenotype described in this report.

Background: Embedded approaches to implementation research (IR), whereby health system decision-makers participate actively in the research process, are gaining traction as effective approaches to optimise the delivery of health programmes and policies. However, the evidence base on the processes and effectiveness of such collaborative research remains inchoate. Standardised approaches to evaluate these initiatives are needed to identify core elements of 'embeddedness', unveil the underlying pathways of change, and assess contribution to evidence uptake in decision-making and overall outcomes of effect. The framework presented in this paper responds to this need, designed to guide the systematic evaluation of embedded IR., Methods: This evaluation framework for embedded IR approaches is based on the experience of a joint initiative by the Pan American Health Organization/Alliance for Health Policy and Systems Research, which has supported 19 IR grants in 10 Latin American and Caribbean countries from 2014 to 2017. The conceptualisation of this framework drew on various sources of information, including empirical evidence and conceptual insights from the literature, interviews with content experts, and a prospective evaluation of the 2016 cohort that included semi-structured key informant interviews, document analysis, and a research team survey to examine key aspects of embedded research., Results: We developed a widely applicable conceptual framework to guide the evaluation of embedded IR in various contexts. Focused on uncovering how this collaborative research approach influences programme improvement, it outlines expected processes and intermediate outcomes. It also highlights constructs with which to assess 'embeddedness' as well as critical contextual factors. The framework is intended to provide a structure by which to systematically examine such embedded research initiatives, proposing three key stages of evidence-informed decision-making - co-production of evidence, engagement with research, and enactment of programme changes., Conclusion: Rigorous evaluation of embedded IR is needed to build the evidence on its processes and effectiveness in influencing decision-making. The evaluation framework presented here addresses this gap with consideration of the complexity of such efforts. Its applicability to similar initiatives is bolstered by virtue of being founded on real-world experience; its potential to contribute to a nuanced understanding of embedded IR is significant.

Background: Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity., Methods/design: This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression-Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18-65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up., Discussion: This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients., Trial Registration: ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018.

Background: Ectodermal dysplasias (ED) are a group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives. An attenuated phenotype is considered a non-syndromic trait when the patient is affected by only one impaired ectodermal structure, such as in non-syndromic tooth agenesis (NSTA) disorder. Hypohidrotic ectodermal dysplasia (HED) is the most highly represented ED. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common subtype, with an incidence of 1/50,000-100,000 males, and is associated with the EDA gene (Xq12-q13.1); the dominant and recessive subtypes involve the EDAR (2q13) and EDARADD (1q42.3) genes, respectively. The WNT10A gene (2q35) is associated more frequently with NSTA. Our goal was to determine the mutational spectrum in a cohort of 72 Spanish patients affected by one or more ectodermal derivative impairments referred to as HED (63/72) or NSTA (9 /72) to establish the prevalence of the allelic variants of the four most frequently associated genes. Sanger sequencing of the EDA, EDAR, EDARADD and WNT10A genes and multiplex ligation-dependent probe amplification (MLPA) were performed., Results: A total of 61 children and 11 adults, comprising 50 males and 22 females, were included. The average ages were 5.4 and 40.2 years for children and adults, respectively. A molecular basis was identified in 51/72 patients, including 47/63 HED patients, for whom EDA was the most frequently involved gene, and 4/9 NSTA patients, most of whom had variants of WNT10A. Among all the patients, 37/51 had variants of EDA, 8/51 had variants of the WNT10A gene, 4/51 had variants of EDAR and 5/51 had variants of EDARADD. In 42/51 of cases, the variants were inherited according to an X-linked pattern (27/42), with the remaining showing an autosomal dominant (10/42) or autosomal recessive (5/42) pattern. Among the NSTA patients, 3/9 carried pathogenic variants of WNT10A and 1/9 carried EDA variants. A total of 60 variants were detected in 51 patients, 46 of which were different, and out of these 46 variants, 12 were novel., Conclusions: This is the only molecular study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in HED and 44.4% in NSTA. Twelve novel variants were identified. The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients. Further studies using next generation sequencing (NGS) will help to identify other contributory genes in the remaining uncharacterized Spanish patients.

Background: Blood stream infections (BSIs) are a major cause of morbidity and mortality. The time from taking blood cultures to obtain results of antibiotic sensitivity can be up to five days which impacts patient care. The Alfred 60 AST™ can reduce laboratory time from positive culture bottle to susceptibility results from 16 to 25 h to 5-6 h, transforming patient care. To evaluate the diagnostic accuracy of a rapid antimicrobial susceptibility system, the Alfred 60 AST™, in clinical isolates from patients with BSIs and confirm time to results. 301 Gram-negative and 86 Gram-positive isolates were analysed directly from positive blood culture bottles following Gram staining. Antimicrobial susceptibility results and time-to-results obtained by rapid Alfred 60 AST system and BD Phoenix were compared ., Results: A total of 2196 antimicrobial susceptibility test results (AST) were performed: 1863 Gram-negative and 333 Gram-positive. AST categorical agreement (CA) for Alfred 60 AST™ was 95% (1772/1863) for Gram-negative and 89% (295/333) for Gram-positive isolates. Gram-negative CA: ampicillin 96% (290/301); ciprofloxacin 95% (283/297); ceftriaxone 96% (75/78); meropenem 97% (288/297); piperacillin-tazobactam 95% (280/295); gentamicin 94% (279/297) and amikacin 93% (277/298). The median time to susceptibility results from blood culture flagging positive was 6.3 h vs 20 h (p < 0.01) for Alfred system vs BD Phoenix™., Conclusion: Alfred 60 AST system greatly reduced time to antimicrobial susceptibility results in Gram-negative and Gram-positive BSIs with good performance and cost, particularly for Gram-negative bacteraemia.

Background: The objective of this study was to obtain utilities by means of EQ-5D-5L for different health states in patients with knee osteoarthritis (KOA) or hip osteoarthritis (HOA) in Spain, and to compare these values with those used in foreign studies with the aim of discussing their transferability for their use in economic evaluations conducted in Spain., Methods: Primary study: Observational prospective study of KOA or HOA patients in Spain. Sociodemographic and clinical characteristics were collected to characterize the sample. Utilities were elicited using the EQ-5D-5L questionnaire. ANOVA and bivariable analyses were conducted to identify differences between health states., Literature Review: Using the bibliographic databases NSH EED and CEA Registry, we conducted searches of model-based cost utilities analyses of technologies in KOA or HOA patients. Health states and utilities were extracted and compared with values obtained from the Spanish sample., Results: Three hundred ninety-seven subjects with KOA and 361 subjects with HOA were included, with average utilities of 0.544 and 0.520, respectively. In both samples, differences were found in utilities according to level of pain, stiffness and physical function (WOMAC) and severity of symptoms (Oxford scales), so that the worst the symptoms, the lower the utilities. The utilities after surgery were higher than before surgery. Due to limitations from our study related to sample size and observational design, it was not possible to estimate utilities for approximately half the health states included in the published models because they were directly related to specific technologies. For almost 100% of health states of the selected studies we obtained very different utilities from those reported in the literature., Conclusions: To our knowledge this is the first article with detailed utilities estimated using the EQ-5D-5L in Spain for KOA and HOA patients. In both populations, utilities are lower for worse health states in terms of level of pain, stiffness and physical function according to WOMAC, and according to the Oxford scales. Most utilities obtained from the Spanish sample are lower than those reported in the international literature. Further studies estimating utilities from local populations are required to avoid the use of foreign sources in economic evaluations.