AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.

This study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the DMPK gene, leading to variable clinical manifestations by depleting muscleblind-like splicing regulator protein MBNL1. AntimiRs targeting natural repressors miR-23b and miR-218 boost MBNL1 expression but must be optimized for a better pharmacological profile in humans. In untreated cells, miR-23b and miR-218 were up-regulated, which correlated with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG expansions in DMPK. AntimiR treatment improved RNA toxicity readouts and corrected regulated exon inclusions and myoblast defects such as fusion index and myotube area across CTG expansions. Unexpectedly, the treatment also reduced DMPK transcripts and ribonuclear foci. A leading antimiR reversed 68% of dysregulated genes. This study highlights the potential of antimiRs to treat various DM1 forms across a range of repeat sizes and genetic backgrounds by mitigating MBNL1 sequestration and enhancing protein synthesis.

Air pollution and children's mental health in rural areas: compositional spatio-temporal model.

Air pollution stands as an environmental risk to child mental health, with proven relationships hitherto observed only in urban areas. Understanding the impact of pollution in rural settings is equally crucial. The novelty of this article lies in the study of the relationship between air pollution and behavioural and developmental disorders, attention deficit hyperactivity disorder (ADHD), anxiety, and eating disorders in children below 15 living in a rural area. The methodology combines spatio-temporal models, Bayesian inference and Compositional Data (CoDa), that make it possible to study areas with few pollution monitoring stations. Exposure to nitrogen dioxide (NO2), ozone (O3), and sulphur dioxide (SO2) is related to behavioural and development disorders, anxiety is related to particulate matter (PM10), O3 and SO2, and overall pollution is associated to ADHD and eating disorders. To sum up, like their urban counterparts, rural children are also subject to mental health risks related to air pollution, and the combination of spatio-temporal models, Bayesian inference and CoDa make it possible to relate mental health problems to pollutant concentrations in rural settings with few monitoring stations. Certain limitations persist related to misclassification of exposure to air pollutants and to the covariables available in the data sources used.

Comparing temporal changes and predictors of different types of mental health and socio-emotional wellbeing outcomes during COVID-19: an overlapping panel study of Spanish residents.

OBJECTIVES: Few panel studies have investigated how different types of mental health (MH) and socio-emotional wellbeing (SEW) outcomes have changed during the pandemic and if their burden has been equally distributed at the population-level. We aimed to examine temporal changes in these outcomes and their socio-ecological predictors using panel data. STUDY DESIGN: Longitudinal population-based survey with overlapping panels. METHODS: Analyses were carried out using four measurements of data from the Health and Social Survey (April 2020 to April 2021). Participants included Andalusian (Spanish) residents aged 16 years or older who participated in all four measurements (n = 1223). Seven dichotomous MH and SEW outcomes, as well as several socio-ecological predictors informed by a conceptual model, were examined in descriptive and multivariate analyses. RESULTS: Unadjusted odds of regular/bad perceived mental health (vs. excellent/very good/good), low socio-emotional wellbeing (vs. regular), low happiness (vs. regular), and feeling anxious (vs. not feeling anxious) decreased significantly from the first to the second measurement; however, in the fourth, low socio-emotional wellbeing significantly increased while low optimism decreased. Considering varying coefficients, objectively measured COVID-19 status and self-reported severity levels of the infection were statistically significant. Health status, social support, and household financial difficulty predicted higher adjusted odds in most of the seven assessed outcomes. CONCLUSIONS: Significant temporal variations in MH and SEW outcomes, along with their predictors, were observed during the first year of the pandemic. Some of these outcomes worsened as the pandemic progressed, whereas others improved. Findings also suggest that some individuals such as those experiencing poor health, limited social support, and low socioeconomic status are disproportionately impacted.

Genetic diversity and cross-species transmissibility of bat-associated picornaviruses from Spain.

BACKGROUND: Emerging zoonotic diseases arise from cross-species transmission events between wild or domesticated animals and humans, with bats being one of the major reservoirs of zoonotic viruses. Viral metagenomics has led to the discovery of many viruses, but efforts have mainly been focused on some areas of the world and on certain viral families. METHODS: We set out to describe full-length genomes of new picorna-like viruses by collecting feces from hundreds of bats captured in different regions of Spain. Viral sequences were obtained by high-throughput Illumina sequencing and analyzed phylogenetically to classify them in the context of known viruses. Linear discriminant analysis (LDA) was performed to infer likely hosts based on genome composition. RESULTS: We found five complete or nearly complete genomes belonging to the family Picornaviridae, including a new species of the subfamily Ensavirinae. LDA suggested that these were true vertebrate viruses, rather than viruses from the bat diet. Some of these viruses were related to picornaviruses previously found in other bat species from distant geographical regions. We also found a calhevirus genome that most likely belongs to a proposed new family within the order Picornavirales, and for which genome composition analysis suggested a plant host. CONCLUSIONS: Our findings describe new picorna-like viral species and variants circulating in the Iberian Peninsula, illustrate the wide geographical distribution and interspecies transmissibility of picornaviruses, and suggest new hosts for calheviruses.

Association between ultraprocessed food consumption and excess adiposity in children and adolescents: A systematic review.

Ultraprocessed foods (UPF) consumption is associated with excess adiposity in adults, but this linkage remains unclear among children and adolescents. The present systematic review sought to address this research gap. Publications up to November 2023 were retrieved from PubMed, Web of Science, and Scopus databases. Outcomes included overweight/obesity anthropometric and body composition indicators; the exposure was UPF consumption based on the NOVA classification system. The review included 23 studies (i.e., 8 cohort and 15 cross-sectional); approximately half were carried out in Brazil. Inconclusive and heterogeneous evidence exists as few cohort studies found positive/mixed associations between UPF consumption and excess adiposity in pediatric populations, whereas most cross-sectional studies reported null associations. Such inconsistencies may be attributed to underlying methodological issues, especially heterogeneity in the outcomes assessed and UPF consumption operationalization and/or categorization. Future studies should adopt longitudinal designs with sufficiently extended follow-up periods, account for relevant confounding factors, employ validated and standardized measurement tools to assess dietary exposure, ensure consistent operationalization of variables, and encompass diverse geographic contexts. Ultimately, strengthening the quality of existing research evidence may better inform current and forthcoming policy and practice interventions aimed at mitigating the increasing prevalence of overweight/obesity in childhood and across the life course.

Impacts of COVID-19 on clinical indicators and mortality in patients with chronic conditions in Catalonia, Spain: A retrospective population-based cohort study.

Background: The reallocation of health care services during the coronavirus disease 2019 (COVID-19) pandemic disrupted the continuity of primary care. This study examines the repercussions of the COVID-19 pandemic on clinical indicators within the Catalan population, emphasising individuals with chronic conditions. It provides insights into mortality and transfer rates considering intersectional perspectives. Methods: We designed a retrospective, observational population-based cohort study based on routinely collected data from January 2015 to June 2021 for all individuals available in the Information System for Research in Primary Care (Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP)), the largest public primary care database in Catalonia, Spain. We included 6 301 095 individuals, constituting 81.6% of Catalonia's population in 2020. To perform a repeated measurements analysis of the indicators, we focussed on individuals who had one or more indicators in both the pre-pandemic (January 2015 to March 2020) and pandemic periods (March 2020 to June 2021), and those diagnosed with type 2 diabetes mellitus (T2D), high blood pressure, and heart failure. We selected key clinical indicators for analysis, including systolic and diastolic blood pressure, body mass index (BMI), cholesterol (total, high, and low-density lipoprotein), triglycerides, glycosylated haemoglobin, the Barthel index, and cardiovascular risk (Registre Gironí del cor (REGICOR) index). Results: Mortality and transfer rates increased during the pandemic, contributing to a decline in the active population in the public health system. We also observed a reduction in pandemic period prevalence of patients with chronic conditions: -26.7% for heart failure, -15.1% for high blood pressure, and -14.6% for T2D. In both pre-pandemic and pandemic periods, 1 632 013 subjects had at least one clinical indicator record. Clinical indicators worsened in patients diagnosed with chronic conditions during the pandemic. Most indicators worsened, with differences between men and women (+9.4% vs +3.7% for the REGICOR index and -14.1% vs -16.6% for the Barthel index in men and in women, respectively), and to a similar extent (or greater in some cases) in individuals without these conditions. Conclusions: We used longitudinal data to assess the repercussions of the COVID-19 pandemic on population health while considering a wide range of clinical indicators and socioeconomic determinants. Our analysis shows a deterioration in clinical indicators during the pandemic, particularly in cardiometabolic factors, underscoring the importance of continuous primary care for individuals with chronic conditions.

Cell type-specific adaptation of the SARS-CoV-2 spike.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can infect various human tissues and cell types, principally via interaction with its cognate receptor angiotensin-converting enzyme-2 (ACE2). However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of key entry factors. After twenty passages of a spike-expressing recombinant vesicular stomatitis virus (VSV), cell-type-specific phenotypic changes were observed and sequencing allowed the identification of sixteen adaptive spike mutations. We used VSV pseudotyping to measure the entry efficiency, ACE2 affinity, spike processing, TMPRSS2 usage, and entry pathway usage of all the mutants, alone or in combination. The fusogenicity of the mutant spikes was assessed with a cell-cell fusion assay. Finally, mutant recombinant VSVs were used to measure the fitness advantage associated with selected mutations. We found that the effects of these mutations varied across cell types, both in terms of viral entry and replicative fitness. Interestingly, two spike mutations (L48S and A372T) that emerged in cells expressing low ACE2 levels increased receptor affinity, syncytia induction, and entry efficiency under low-ACE2 conditions. Our results demonstrate specific adaptation of the SARS-CoV-2 spike to different cell types and have implications for understanding SARS-CoV-2 tissue tropism and evolution.

Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain.

OBJECTIVE: To determine if a 4-week manual therapy treatment restores normal functioning of central pain processing mechanisms in non-specific chronic neck pain (NSCNP), as well as the existence of a possible relationship between changes in pain processing mechanisms and clinical outcome. DESIGN: Cohort study. METHODS: Sixty-three patients with NSCNP, comprising 79% female, with a mean age of 45.8 years (standard deviation: 14.3), received four treatment sessions (once a week) of manual therapy including articular passive mobilizations, soft tissue mobilization and trigger point treatment. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM) and temporal summation of pain (TSP) were evaluated at baseline and after treatment completion. Therapy outcome was measured using the Global Rating of Change Scale (GROC), the Neck disability Index (NDI), intensity of pain during the last 24 hours, Tampa Scale of Kinesiophobia (TSK) and Pain Catastrophizing Scale (PCS). Two sets of generalized linear mixed models with Gaussian response and the identity link were employed to evaluate the effect of the intervention on clinical, psychological and psychophysical measures and the association between psychophysical and clinical outcomes. RESULTS: Following treatment, an increased CPM response (Coefficient: 0.89; 95% credibility interval = 0.14 to 1.65; P = .99) and attenuated TSP (Coefficient: -0.63; 95% credibility interval = -0.82 to -0.43; P = 1.00) were found, along with amelioration of pain and improved clinical status. PPTs at trapezius muscle on the side of neck pain were increased after therapy (Coefficient: 0.22; 95% credibility interval = 0.03 to 0.42; P = .98), but not those on the contralateral trapezius and tibialis anterior muscles. Only minor associations were found between normalization of TSP/CPM and measures of clinical outcome. CONCLUSION: Clinical improvement after manual therapy is accompanied by restoration of CPM and TSP responses to normal levels in NSCNP patients. The existence of only minor associations between changes in central pain processing and clinical outcome suggests multiple mechanisms of action of manual therapy in NSCNP.

Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) - study protocol.

INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

Multimorbidity patterns and disability and healthcare use in Europe: do the associations change with the regional socioeconomic status?

Multimorbidity, the concurrence of several chronic conditions, is a rising concern that increases the years lived with disability and poses a burden on healthcare systems. Little is known on how it interacts with socioeconomic deprivation, previously associated with poor health-related outcomes. We aimed to characterize the association between multimorbidity and these outcomes and how this relationship may change with socioeconomic development of regions. 55,915 individuals interviewed in 2017 were drawn from the Survey of Health, Ageing and Retirement in Europe, a population-based study. A Latent Class Analysis was conducted to fit multimorbidity patterns based on 16 self-reported conditions. Physical limitation, quality-of-life and healthcare utilization outcomes were regressed on those patterns adjusting for additional covariates. Those analyses were then extended to assess whether such associations varied with the region socioeconomic status. We identified six different patterns, labelled according to their more predominant chronic conditions. After the "healthy" class, the "metabolic" and the "osteoarticular" classes had the best outcomes involving limitations and the lowest healthcare utilization. The "neuro-affective-ulcer" and the "several conditions" classes yielded the highest probabilities of physical limitation, whereas the "cardiovascular" group had the highest probability of hospitalization. The association of multimorbidity over physical limitations appeared to be stronger when living in a deprived region, especially for metabolic and osteoarticular conditions, whereas no major effect differences were found for healthcare use. Multimorbidity groups do differentiate in terms of limitation and healthcare utilization. Such differences are exacerbated with socioeconomic inequities between regions even within Europe.

Peptide-conjugated antimiRs improve myotonic dystrophy type 1 phenotypes by promoting endogenous MBNL1 expression.

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the DMPK gene that generates toxic RNA with a myriad of downstream alterations in RNA metabolism. A key consequence is the sequestration of alternative splicing regulatory proteins MBNL1/2 by expanded transcripts in the affected tissues. MBNL1/2 depletion interferes with a developmental alternative splicing switch that causes the expression of fetal isoforms in adults. Boosting the endogenous expression of MBNL proteins by inhibiting the natural translational repressors miR-23b and miR-218 has previously been shown to be a promising therapeutic approach. We designed antimiRs against both miRNAs with a phosphorodiamidate morpholino oligonucleotide (PMO) chemistry conjugated to cell-penetrating peptides (CPPs) to improve delivery to affected tissues. In DM1 cells, CPP-PMOs significantly increased MBNL1 levels. In some candidates, this was achieved using concentrations less than two orders of magnitude below the median toxic concentration, with up to 5.38-fold better therapeutic window than previous antagomiRs. In HSALR mice, intravenous injections of CPP-PMOs improve molecular, histopathological, and functional phenotypes, without signs of toxicity. Our findings place CPP-PMOs as promising antimiR candidates to overcome the treatment delivery challenge in DM1 therapy.

Predictive capacity of FRAX in a spanish region with a hip fracture rate close to the national mean.

BACKGROUND: It is known that standardized incidence rates of hip fracture vary among older people in Spain. So far, the results published on the validation of the FRAX® tool in Spain have suggested that the major osteoporotic fractures (MOFs) risk in our country is underestimated. These studies have practically been based on Spanish cohorts evaluated in Catalonia, a higher hip fracture rate area. The purpose of this study is to analyse the ability of the FRAX® in a Spanish mid-fracture rate population. METHODS: Study design: Retrospective cohort study. MEASURES: MOFs: hip, humerus, wrist, spine fractures. Risk of fracture assessed by calculating odds ratios (ORs). Predictive capacity of FRAX® according to the osteoporotic fractures observed between 2009 and 2018 (ObsFr) to predicted by FRAX® without densitometry in 2009 (PredFr) ratio. RESULTS: 285 participants (156 women, 54.7%) with a mean ± SD of 61.5 ± 14 years. Twenty-four people sustained 27 fractures (15 MOFs). Significant ORs were observed for an age ≥ 65 (2.92; 95% CI, 1.07-7.96), female sex (3.18; 95% CI, 1.24-8.16), rheumatoid arthritis (0.62; 95% CI, 2.03-55.55), proton pump (2.71; 95% CI, 1.20-6.09) and serotonin reuptake (2.51; 95% CI, 1.02-6.16) inhibitors. The ObsFr/PredFr ratio in women were 1.12 (95% CI, 0.95-1.29) for MOFs and 0.47 (95% CI, 0-0.94) for hip fractures. Men had a ratio of 0.57 (95% CI, 0.01-1.14) for MOF, no hip fractures were observed. The ratios for the overall group were 1.29 (95% CI, 1.12-1.48) for MOFs and 0.70 (95% CI, 0.22-1.17) for hip fractures. CONCLUSIONS: FRAX® accurately predicted MOFs in women population with a hip fracture incidence rate close to the national mean compared to previous studies conducted in higher incidence regions in Spain.

Epidemiological and clinical profile of amyotrophic lateral sclerosis in Ethiopia: a 5-year multicenter retrospective study.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in progressive weakness of skeletal muscles including respiratory muscles. Epidemiological and clinical aspects of ALS are derived from a few world regions with very little representation of low- and middle-income countries. We therefore set out to determine the epidemiological and clinical phenotype of individuals with ALS in Ethiopia. Methods: Multicenter retrospective analysis was conducted using clinical records from ALS patients seen in Ethiopia at Tikur Anbessa Specialized Hospital and Yehuleshet specialty clinic between January 2016 and August 2021. The data collected included clinical characteristics, disease-related symptoms, a revised ALS functional rating scale, and medications. Results: Patients in Ethiopia had a younger age of onset with a mean age of disease onset of 51.9 years. 2.9% of patients had juvenile ALS, and the male-to-female ratio was almost 2:1. 4.9% had a positive family history of the disease. 68% of patients had spinal region involvement at onset, while 32% had bulbar region involvement at onset. Riluzole was used by 31% of ALS patients. 20.6% of patients had some respiratory symptoms, but none received a standard respiratory function assessment. 33.3% of patients were wheelchair-bound. Conclusion: In this retrospective study spanning 5 years, we examined the clinical phenotype of ALS in Ethiopian patients. Our findings suggest that most patients had clinically definite ALS with spinal region involvement. Further research, including genetic and epigenetic information, is necessary to understand the early onset of the disease in Ethiopia.

A 14-Year Longitudinal Analysis of Healthcare Expenditure on Dementia and Related Factors (DEMENCOST Study).

BACKGROUND: The large number of dementia cases produces a great pressure on health and social care services, which requires efficient planning to meet the needs of patients through infrastructure, equipment, and financial, technical, and personal resources adjusted to their demands. Dementia analysis requires studies with a very precise patient characterization of both the disease and comorbidities present, and long-term follow-up of patients in clinical aspects and patterns of resource utilization and costs generated. OBJECTIVE: To describe and quantify direct healthcare expenditure and its evolution from three years before and up to ten years after the diagnosis of dementia, compared to a matched group without dementia. METHODS: Retrospective cohort design with follow-up from 6 to 14 years. We studied 996 people with dementia (PwD) and 2,998 controls matched for age, sex, and comorbidity. This paper adopts the provider's perspective as the perspective of analysis and refers to the costs actually incurred in providing the services. Aggregate costs and components per patient per year were calculated and modelled. RESULTS: Total health expenditure increases in PwD from the year of diagnosis and in each of the following 7 years, but not thereafter. Health status and mortality are factors explaining the evolution of direct costs. Dementia alone is not a statistically significant factor in explaining differences between groups. CONCLUSION: The incremental direct cost of dementia may not be as high or as long as studies with relatively short follow-up suggest. Dementia would have an impact on increasing disease burden and mortality.

Impact of the COVID-19 Pandemic on the Socioeconomic Inequalities in Mortality in Spanish Provinces.

BACKGROUND: Although many studies have assessed the socioeconomic inequalities caused by COVID-19 in several health outcomes, there are numerous issues that have been poorly addressed. For instance, have socioeconomic inequalities in mortality from COVID-19 increased? What impact has the pandemic had on inequalities in specific causes of mortality other than COVID-19? Are the inequalities in COVID-19 mortality different from other causes? In this paper we have attempted to answer these questions for the case of Spain. METHODS: We used a mixed longitudinal ecological design in which we observed mortality from 2005 to 2020 in the 54 provinces into which Spain is divided. We considered mortality from all causes, not excluding, and excluding mortality from COVID-19; and cause-specific mortality. We were interested in analysing the trend of the outcome variables according to inequality, controlling for both observed and unobserved confounders. RESULTS: Our main finding was that the increased risk of dying in 2020 was greater in the Spanish provinces with greater inequality. In addition, we have found that: (i) the pandemic has exacerbated socioeconomic inequalities in mortality, (ii) COVID-19 has led to gender differences in the variations in risk of dying (higher in the case of women) and (iii) only in cardiovascular diseases and Alzheimer did the increased risk of dying differ between the most and least unequal provinces. The increase in the risk of dying was different by gender (greater in women) for cardiovascular diseases and cancer. CONCLUSION: Our results can be used to help health authorities know where and in which population groups future pandemics will have the greatest impact and, therefore, be able to take appropriate measures to prevent such effects.

Housing Supply and How It Is Related to Social Inequalities-Air Pollution, Green Spaces, Crime Levels, and Poor Areas-In Catalonia.

We carried out a search of over 12,000 houses offered on the rental market in Catalonia and assessed the possibility of families below the poverty threshold being able to rent these homes. In this regard, we wanted to evaluate whether the economic situation of families is able to influence their social environment, surroundings, and safety. We observed how their economic situation can allow families the possibility of developing a life without exposure to health risks, and how economic constraints result in disadvantages in several areas of life. The results show how families at risk of poverty live in less favourable conditions and experience a widening of different gaps, with current prices leading to a possible poverty trap for the most disadvantaged groups. The higher the percentage of the population below the threshold, the lower the possibility of not being able to rent a house compared to areas with a lower prevalence of population below the threshold. This association was observed both when considering the risk linearly and non-linearly. Linearly, the probability of not renting a house was reduced by 8.36% for each 1% increase in the prevalence of population at risk of extreme poverty. In the second, third and fourth percentage quartiles, the probability of not being able to rent a house decreased by 21.13%, 48.61%, and 57.79%, respectively. In addition, the effect was different inside and outside of metropolitan areas, with the former showing a decrease of 19.05% in the probability of renting a house, whereas outside metropolitan areas the probability increased by 5.70%.

Repurposing selective serotonin reuptake inhibitors for severity of COVID-19: A population-based study.

The World Health Organization has proposed that a search be made for alternatives to vaccines for the prevention and treatment of COVID-19, with one such alternative being selective serotonin reuptake inhibitors (SSRIs). This study thus sought to assess: the impact of previous treatment with SSRI antidepressants on the severity of COVID-19 (risk of hospitalisation, admission to an intensive care unit [ICU], and mortality), its influence on susceptibility to SARS-CoV-2 and progression to severe COVID-19. We conducted a population-based multiple case-control study in a region in the north-west of Spain. Data were sourced from electronic health records. Adjusted odds ratios (aORs) and 95%CIs were calculated using multilevel logistic regression. We collected data from a total of 86,602 subjects: 3060 cases PCR+, 26,757 non-hospitalised cases PCR+ and 56,785 controls (without PCR+). Citalopram displayed a statistically significant decrease in the risk of hospitalisation (aOR=0.70; 95% CI 0.49-0.99, p = 0.049) and progression to severe COVID-19 (aOR=0.64; 95% CI 0.43-0.96, p = 0.032). Paroxetine was associated with a statistically significant decrease in risk of mortality (aOR=0.34; 95% CI 0.12 - 0.94, p = 0.039). No class effect was observed for SSRIs overall, nor was any other effect found for the remaining SSRIs. The results of this large-scale, real-world data study indicate that, citalopram, could be a candidate drug for being repurposed as preventive treatment aimed at reducing COVID-19 patients' risk of progressing to severe stages of the disease.

APPRAISE-RS: Automated, updated, participatory, and personalized treatment recommender systems based on GRADE methodology.

Purpose: Clinical practice guidelines (CPGs) have become fundamental tools for evidence-based medicine (EBM). However, CPG suffer from several limitations, including obsolescence, lack of applicability to many patients, and limited patient participation. This paper presents APPRAISE-RS, which is a methodology that we developed to overcome these limitations by automating, extending, and iterating the methodology that is most commonly used for building CPGs: the GRADE methodology. Method: APPRAISE-RS relies on updated information from clinical studies and adapts and automates the GRADE methodology to generate treatment recommendations. APPRAISE-RS provides personalized recommendations because they are based on the patient's individual characteristics. Moreover, both patients and clinicians express their personal preferences for treatment outcomes which are considered when making the recommendation (participatory). Rule-based system approaches are used to manage heuristic knowledge. Results: APPRAISE-RS has been implemented for attention deficit hyperactivity disorder (ADHD) and tested experimentally on 28 simulated patients. The resulting recommender system (APPRAISE-RS/TDApp) shows a higher degree of treatment personalization and patient participation than CPGs, while recommending the most frequent interventions in the largest body of evidence in the literature (EBM). Moreover, a comparison of the results with four blinded psychiatrist prescriptions supports the validation of the proposal. Conclusions: APPRAISE-RS is a valid methodology to build recommender systems that manage updated, personalized and participatory recommendations, which, in the case of ADHD includes at least one intervention that is identical or very similar to other drugs prescribed by psychiatrists.

Colchicine and risk of hospitalization due to COVID-19: A population-based study.

Colchicine is one of the most widely studied and best-known anti-inflammatory treatments. This study aimed to assess the effect of colchicine on risk of hospitalization due to COVID-19; and its effect on susceptibility to and severity of the virus in patients with COVID-19. We carried out a population-based case-control study. The following groups were applied: (1) to assess risk of hospitalization, cases were patients with a positive PCR who were hospitalized due to COVID-19, and controls without a positive PCR; (2) to assess susceptibility to COVID-19, cases were patients with a positive PCR (hospitalized and non-hospitalized), and the same controls; (3) to determine potential severity, cases were subjects with COVID-19 hospitalized, and controls patients with COVID-19 nonhospitalised. Different electronic, linked, administrative health and clinical databases were used to extract data on sociodemographic variables, comorbidities, and medications dispensed. The study covered 3060 subjects with a positive PCR who were hospitalized, 26 757 with a positive PCR who were not hospitalized, and 56 785 healthy controls. After adjustment for sociodemographic variables, comorbidities and other treatments, colchicine did not modify risk of hospitalization due to COVID-19 (adjusted odd ratio [OR] 1.08 [95% confidence interval (CI) 0.76-1.53]), patients' susceptibility to contracting the disease (adjusted OR 1.12 (95% CI 0.91-1.37)) or the severity of the infection (adjusted OR 1.03 [95% CI 0.67-1.59]). Our results would neither support the prophylactic use of colchicine for prevention of the infection or hospitalization in any type of patient, nor justify the withdrawal of colchicine treatment due to a higher risk of contracting COVID-19.