Toward Telemonitoring in Immune-Mediated Inflammatory Diseases: Protocol for a Mixed Attention Model Study

Mixed attention model; Rheumatic musculoskeletal diseases; TelemonitoringModelo de atención mixta; Enfermedades musculoesqueléticas reumáticas; TelevigilanciaModel d'atenció mixta; Malalties musculoesquelètiques reumàtiques; TelevigilànciaBackground: Rheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient’s quality of life. Often, delays in outpatient consultations or the patient’s difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self-manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed. Objective: The main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up. Methods: This is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient-reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self-assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app. Results: Participant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025. Conclusions: This paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMDs.This work was supported by: Fondo para la Investigación Sanitaria, Instituto de Salud Carlos III (PI22/00777)

Toward Telemonitoring in Immune-Mediated Inflammatory Diseases: Protocol for a Mixed Attention Model Study

Background: Rheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient's quality of life. Often, delays in outpatient consultations or the patient's difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self -manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed. Objective: The main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up. Methods: This is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient -reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self -assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app. Results: Participant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025. Conclusions: This paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMD

Sedimentation and biomineralization processes in Las Eras Lake (Coca-Olmedo wetland)

La Laguna de Las Eras es uno de los pequeños y someros cuerpos de agua, que forman el humedal de la zona Coca-Olmedo (cuenca del Duero), caracterizado por su elevada alcalinidad, lo que constituye un rasgo singular dentro de Europa. La laguna presenta una salmuera de tipo Na-Mg-Cl- SO4 y su superficie está colonizada por tapices microbianos, donde se desarrollan estructuras sedimentarias inducidas por los microorganismos (MISS). Se reconocen diversos minerales autigénicos asociados a los tapices: thenardita, hidromagnesita, sulfatos y fosfatos magnésicos, azufre y halita. Junto a éstos destacan, por ser carbonatos atípicos en Europa, natrón y trona. El estudio petrográfico de los precipitados revela que éstos guardan una estrecha relación con las estructuras microbianas, sugiriendo cierta influencia de los microorganismos en la precipitación mineral. Los tapices microbianos de la laguna de Las Eras constituyen buenos análogos para comprender los procesos geobiológicos y ahondar en la reconstrucción paleoambiental de los lagos alcalinos que han existido desde el ArcaicoLas Eras Lake is one of the small and shallow bodies of water, which form the highly alkaline Coca-Olmedo wetland (Duero Basin), a unique feature within Europe. The lake brine is a Na-Mg-Cl-SO4 type. The lake hosts benthic microbial mats and its surface shows microbially influenced sedimentary structures (MISS). Associated with the microbial mats, several authigenic minerals are recognized such as thenardite, hydromagnesite, magnesium- bearing sulphate and phosphate, halite and sulphur.Among these we highlight the occurrence of natron and trona because the sodium-bearing carbonates are uncommon in the european region. The scanning electron microscopy study reveals that the minerals are closely related to microbial structures, suggesting some influence of microorganisms in the mineral precipitation. Recent microbial mats as those hosted in Las Eras Lake are good analogues for understanding geobiological processes. Knowledge of these processes provides a model for paleoenvironmental reconstruction of alkaline endorheic lakes that have existed since the Arc

Sedimentation and biomineralization processes in Las Eras Lake (Coca-Olmedo wetland)

La Laguna de Las Eras es uno de los pequeños y someros cuerpos de agua, que forman el humedal de la zona Coca-Olmedo (cuenca del Duero), caracterizado por su elevada alcalinidad, lo que constituye un rasgo singular dentro de Europa. La laguna presenta una salmuera de tipo Na-Mg-ClSO4 y su superficie está colonizada por tapices microbianos, donde se desarrollan estructuras sedimentarias inducidas por los microorganismos (MISS). Se reconocen diversos minerales autigénicos asociados a los tapices: thenardita, hidromagnesita,sulfatos y fosfatos magnésicos, azufre y halita. Junto a éstos destacan, por ser carbonatos atípicos en Europa, natrón y trona. El estudio petrográfico de los precipitados revela que éstos guardan una estrecha relación con las estructuras microbianas, sugiriendo cierta influencia de los microorganismos en la precipitación mineral.Los tapices microbianos de la laguna de Las Eras constituyen buenos análogos para comprender los procesos geobiológicos y ahondar en la reconstrucción paleoambiental de los lagos alcalinos que han existido desde el Arcaico.Las Eras Lake is one of the small and shallow bodies of water, which form the highly alkaline Coca-Olmedo wetland (Duero Basin), a unique feature within Europe. The lake brine is a Na-Mg-Cl-SO4 type. The lake hosts benthic microbial mats and its surface shows microbially influenced sedimentary structures (MISS). Associated with the microbial mats, several authigenic minerals are recognized such as thenardite, hydromagnesite, magnesium-bearing sulphate and phosphate, halite and sulphur.Among these we highlight the occurrence of natron and trona because the sodium-bearing carbonates are uncommon in the european region. The scanning electron microscopy study reveals that the minerals are closely related to microbial structures,suggesting some influence of microorganisms in the mineral precipitation. Recent microbial mats as those hosted in Las Eras Lake are good analogues for understanding geobiological processes. Knowledge of these processes provides a model for paleoenvironmental reconstruction of alkaline endorheic lakes that have existed since the Archean.Depto. de Biodiversidad, Ecología y EvoluciónFac. de Ciencias BiológicasTRUEMinisterio de Economía y Competitividad (MINECO)pu

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies

BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.Instituto de Salud Carlos III [PI11/0699, PI14/0967, PI14/01477, RD012/0042/0029, RD012/0042/0049, RD012/0042/0066, RD12/0042/0069]; Spanish Ministry of Economy and Competitiveness [SAF2015-71863-REDT]; Plan Nacional de I+D+I; Plan Estatalde I+D+I, European Regional Development Fund; Health in Code SLS

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality