Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort.

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.

Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial.

BACKGROUND: Cardiovascular (CV) polypills are a useful baseline treatment to prevent CV diseases by combining different drug classes in a single pill to simultaneously target more than one risk factor. The aim of the present trial was to determine whether the treatment with the CNIC-polypill was at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDL-c) and systolic BP (SBP) values in subjects at high or very high risk without a previous CV event. METHODS: The VULCANO was an international, multicentre open-label trial involving 492 participants recruited from hospital clinics or primary care centres. Patients were randomised to the CNIC-polypill -containing aspirin, atorvastatin, and ramipril- or usual care. The primary outcome was the comparison of the mean change in LDL-c and SBP values after 16 weeks of treatment between treatment groups. RESULTS: The upper confidence limit of the mean change in LDL-c between treatments was below the prespecified margin (10 mg/dL) and above zero, and non-inferiority and superiority of the CNIC-polypill (p = 0.0001) was reached. There were no significant differences in SBP between groups. However, the upper confidence limit crossed the prespecified non-inferiority margin of 3 mm Hg. Significant differences favoured the CNIC-polypill in reducing total cholesterol (p = 0.0004) and non-high-density lipoprotein cholesterol levels (p = 0.0017). There were no reports of major bleeding episodes. The frequency of non-serious gastrointestinal disorders was more frequent in the CNIC-polypill arm. CONCLUSION: The switch from conventional treatment to the CNIC-polypill approach was safe and appears a reasonable strategy to control risk factors and prevent CVD. Trial registration This trial was registered in the EU Clinical Trials Register (EudraCT) the 20th February 2017 (register number 2016-004015-13; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-004015-13 ).

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study.

BACKGROUND: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. OBJECTIVE: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. METHODS: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. RESULTS: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. CONCLUSIONS: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

[Adjusted morbidity groups: Characteristics and comorbidities in patients with chronic conditions according to their risk level in Primary Care]. / Grupos de morbilidad ajustados: características y comorbilidades de los pacientes crónicos según nivel de riesgo en Atención Primaria.

AIMS: To describe the characteristics of patients with chronic conditions according to their risk levels assigned by the adjusted morbidity groups (AMG). To analyse the factors associated with a high risk level and to study their effect. DESIGN: Observational cross-sectional study with an analytical focus. LOCATION: Primary care (PC), Madrid Health Service. PARTICIPANTS: Population of 18,107 patients stratified by their risk levels with the AMG in the computerised clinical records of Madrid PC. MAIN MEASUREMENTS: The variables studied were: socio-demographic, clinical-nursing care and use of services. Univariate, bivariate, and multivariate analysis were performed. RESULTS: Of the 18,107 patients, 9,866(54.4%) were identified as chronic patients, with 444 (4.5%) stratified as high risk, 1784 (18,1%) as medium risk, and 7,638 (77.4%) as low risk. The high risk patients, compared with medium and low risk, had an older mean age [77.8 (SD=12.9), 72.1 (SD=12.9), 50.6 (SD=19.4)], lower percentage of women (52.3%, 65%, 61.1%), a higher number of chronic diseases [6.7 (SD=2.4), 4.3 (SD=1.5), 1.9 (SD=1.1)], polymedication (79.1%, 43.3%, 6.2%), and contact with PC [33.9 (28), 21.4 (17.3), 7.9 (9.9)] (P<.01). In the multivariate analysis, the high risk level was independently related to age>65 [1.43 (1.03-1.99), male gender (OR=3.46, 95% CI=2.64-4.52), immobility (OR=6.33, 95% CI=4.40-9.11), number of chronic conditions (OR=2.60, 95% CI=2.41-2.81), and PC contact>7 times (OR=1.95, 95% CI=1.36-2.80)] (P<.01). CONCLUSIONS: More than half of the population is classified by the AMG as a chronic, and it is stratified into 3 risk levels that show differences in gender, age, functional impairment, need for care, morbidity, complexity, and use of Primary Care services. Age>65, male gender, immobility, number of chronic conditions, and contact with PC>7 times were the factors associated with high risk.

[Perception of physicians on factors that influence the choice of a dicoumarin or a new oral anticoagulant in patients with non-valvular atrial fibrillation]. / Percepción de los médicos sobre los factores que influyen en la elección de un dicumarínico o de un nuevo anticoagulante oral en pacientes con fibrilación auricular no valvular.

AIMS: Recent studies have demonstrated the efficacy and safety of new oral anticoagulant drugs for the prevention of thromboembolic events in patients with non-valvular atrial fibrillation. Our aim was to evaluate the factors that can influence physicians in their choice between a classic and a new anticoagulant in these patients. DESIGN: Several variables of interest were discussed and analysed using a WorkmatTM methodology. SITES: Six regional meetings were held in Spain (East, Catalonia, Andalusia-Extremadura, Madrid, North-east, and North of Spain). PARTICIPANTS: Meetings were attended by 39 specialists (cardiologists, neurologists, haematologists, internists, and emergency and Primary Care physicians). MEASUREMENTS: Each participant graded their level of agreement, with a score from 1 to 10, on every analysed variable. RESULTS: A new anticoagulant drug was preferred in patients with previous failure of dicoumarin therapy (9.7±0.5), high haemorrhagic risk (8.7±1), prior bleeding (7.8±1.5), and high thrombotic risk (7.7±1.2). Dicoumarins were preferred in cases of severe (1.2±0.4) or moderate (4.2±2.5) kidney failure, good control with dicoumarins (2.3±1.5), cognitive impairment (3.2±3), and low haemorrhagic risk (4.3±3). Age, sex, weight, cost of drug, polymedication, and low thrombotic risk achieved intermediate scores. There were no differences between the different specialists or Spanish regions. CONCLUSIONS: The presence of a high thrombotic or haemorrhagic risk and the failure of previous dicoumarin therapy lead to choosing a new oral anticoagulant in patients with non-valvular atrial fibrillation, while kidney failure, cognitive impairment, good control with dicoumarins, and a low bleeding risk predispose to selecting a classic dicoumarin anticoagulant.

Antithrombotic treatment in elderly patients with atrial fibrillation: a practical approach.

BACKGROUND: Atrial fibrillation (AF) in the elderly is a complex condition. It has a direct impact on the underuse of antithrombotic therapy reported in this population. DISCUSSION: All patients aged ≥75 years with AF have an individual yearly risk of stroke >4 %. However, the risk of hemorrhage is also increased. Moreover, in this population it is common the presence of other comorbidities, cognitive disorders, risk of falls and polymedication. This may lead to an underuse of anticoagulant therapy. Direct oral anticoagulants (DOACs) are at least as effective as conventional therapy, but with lesser risk of intracranial hemorrhage. The simplification of treatment with these drugs may be an advantage in patients with cognitive impairment. The great majority of elderly patients with AF should receive anticoagulant therapy, unless an unequivocal contraindication. DOACs may be the drugs of choice in many elderly patients with AF. In this manuscript, the available evidence about the management of anticoagulation in elderly patients with AF is reviewed. In addition, specific practical recommendations about different controversial issues (i.e. patients with anemia, thrombocytopenia, risk of gastrointestinal bleeding, renal dysfunction, cognitive impairment, risk of falls, polymedication, frailty, etc.) are provided.

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish Society of Internal Medicine.

BACKGROUND: Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION: Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY: In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

Implementation of a virtual community of practice to promote the empowerment of middle-aged people with multimorbidity: study protocol of a randomised controlled trial.

INTRODUCTION: Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions. METHODS AND ANALYSIS: People aged 30-60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community. ETHICS AND DISSEMINATION: The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences. TRIAL REGISTRATION NUMBER: NCT06046326.

Clinical characteristics associated with elevated levels of lipoprotein(a) in patients with vascular risk.

Objectives: Lipoprotein(a) (Lp(a)) is increasingly used in the evaluation of patients with vascular risk due to its association with cardiovascular events. The purpose of this study was to identify the clinical characteristics of patients with elevated levels of Lp(a) attended in an outpatient vascular risk unit. Methods: An observational, retrospective study was conducted to assess the clinical characteristics of patients with elevated levels of Lp(a) (≥50 mg/dL), as compared to patients with normal values (<50 mg/dL). The sample was composed of 878 patients identified as having a high vascular risk due to a diagnosis of vascular disease, attended in a vascular risk unit between 2021 and 2022. Results: The highest levels of Lp(a) were independently associated with a higher probability of having a history of peripheral arterial disease (p=0.024), polygenic familial hypercholesterolemia (PH, p=0.030) and combined familial hypercholesterolemia (CFH, p=0.015); and using PCSK9 inhibitor treatment (p=0.029) and combination therapy with statins and ezetimibe (p=0.018). In contrast, there were no significant differences in relation to familial history of early cardiovascular disease (p=0.143) or personal history of cardiovascular disease (p=0.063), which contrasts with other series. Conclusions: Elevated levels of Lp(a) were associated with a history of peripheral arterial disease, diagnosis of FHP and CFH, and need for more intense lipid-lowering treatments.

GLP-1 RAs in Spain: A Short Narrative Review of Their Use in Real Clinical Practice.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of drugs with potent glucose-lowering activity. Additionally, some GLP-1 RAs have demonstrated cardiovascular and renal benefits. Current guidelines recommend their use in patients with type 2 diabetes (T2D) at high risk of or with established cardiovascular disease (CVD), regardless of glycaemic control, with lifestyle modification and metformin. However, several studies have recently highlighted the limited number of patients with T2D benefiting from these medications worldwide. Given the huge burden of CVD among patients with T2D, efforts should be made to bring clinical practice closer to expert guidelines. This review describes the current situation of GLP-1 RA use in Spain and the reasons behind the gap between guidelines and real-world practice and suggests possible solutions. Administrative issues, lack of awareness of the cardiovascular benefits, clinical inertia, rejection of injectable medication and costs could be some of the reasons for the current situation. Possible strategies that could help to close the gap include encouraging a multidisciplinary approach to the treatment of diabetes which involves cardiologists, endocrinologists, nephrologists, primary care providers and pharmacists; improved awareness of comorbidities and earlier evaluation and treatment or risks; and better education of healthcare providers regarding the cardioprotective benefits of these drugs.

The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of drugs that can be beneficial for patients with type 2 diabetes who are at high risk of cardiovascular complications, such as heart attacks. For this reason, the current clinical guidelines strongly recommend their use in these patients. Unfortunately, many patients with type 2 diabetes and high cardiovascular risk still do not benefit from these drugs. This review analyses the reasons for this situation in Spain, and proposes some possible solutions. The reasons for the low use of GLP-1 RAs could be related to doctors not updating a patient's diabetes medicine as often as they should, lack of awareness about the cardiovascular benefits of these drugs, fear of medicines that involve needles, administrative issues, and costs. Some of the possible strategies to improve the use of GLP-1 RAs among patients with type 2 diabetes with high cardiovascular risk could be to foster greater cooperation among specialists, increase awareness of the need to treat cardiovascular risk in patients with diabetes, and better education of doctors regarding the benefits of these drugs.

Recommendations for the care of patients with cardiovascular disease in health emergency situations: a call to action.

COVID-19 has had a negative impact on the health care of patients with cardiovascular disease and patients at high risk of cardiovascular disease. The restrictions affecting access to the health care system have conditioned the care received, resulting in poorer control and a higher risk of events. Taking action to improve the care provided during health emergencies is mandatory. It is important to promote the development of telemedicine and patient empowerment by fostering health literacy and a higher degree of self-care. In addition, primary care and coordination between health care levels should be improved. Moreover, the simplification and optimization of treatment, for example, using the cardiovascular polypill, have led to an improvement in adherence, better control of vascular risk factors, and a reduced risk of events. The present document provides specific recommendations for improving the care provided to patients under a health emergency.

Adjusted morbidity groups and survival: a retrospective cohort study of primary care patients with chronic conditions.

BACKGROUND: Chronic conditions are one of the main determinants of frailty, functional disability, loss of quality of life and the number one cause of death worldwide. This study aimed to describe the survival of patients with chronic conditions who were followed up in primary care according to the level of risk by adjusted morbidity groups and to analyse the effects of sex, age, clinician and care factors on survival. METHODS: This was a longitudinal observational study of a retrospective cohort of patients with chronic conditions identified by the adjusted morbidity group stratifier of the electronic medical records in a primary health centre of the Region of Madrid, which has an assigned population of 18,107 inhabitants. The follow-up period was from June 2015 to June 2018. A description of survival according to the Kaplan-Meier method and Cox proportional hazards multivariate regression model was used to analyse the effects of sex, age, clinician and care factors. RESULTS: A total of 9,866 patients with chronic conditions were identified; 77.4% (7,638) had a low risk, 18.1% (1,784) had a medium risk, and 4.5% (444) had a high risk according to the adjusted morbidity groups. A total of 477 patients with chronic conditions died (4.8%). The median survival was 36 months. The factors associated with lower survival were age over 65 years (hazard ratio [HR] = 1.3; 95% confidence interval [CI] = 1.1-1.6), receiving palliative care (HR = 3.4; 95% CI = 2.6-4.5), high versus low risk level (HR = 2.4; 95% CI = 1.60-3.7), five chronic conditions or more (HR = 1.5; 95% CI = 1.2-2), complexity index (HR = 1.01; 95% CI = 1.02-1.04) and polymedication (HR = 2.6; 95% CI = 2.0-3.3). CONCLUSIONS: There was a gradual and significant decrease in the survival of patients with chronic conditions according to their level of risk as defined by adjusted morbidity groups. Other factors, such as older age, receiving palliative care, high number of chronic conditions, complexity, and polymedication, had a negative effect on survival. The adjusted morbidity groups are useful in explaining survival outcomes and may be valuable for clinical practice, resource planning and public health research.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

A cluster-randomised clinical trial comparing two cardiovascular health education strategies in a child population: the Savinghearts project.

BACKGROUND: This paper describes a methodology for comparing the effects of an eduentertainment strategy involving a music concert, and a participatory class experience involving the description and making of a healthy breakfast, as educational vehicles for delivering obesity-preventing/cardiovascular health messages to children aged 7-8 years. METHODS/DESIGN: This study will involve a cluster-randomised trial with blinded assessment. The study subjects will be children aged 7-8 years of both sexes attending public primary schools in the Madrid Region. The participating schools (n=30) will be randomly assigned to one of two groups: 1) Group MC, in which the children will attend a music concert that delivers obesity-preventing/cardiovascular health messages, or 2) Group HB, in which the children will attend a participatory class providing the same information but involving the description and making of a healthy breakfast. The main outcome measured will be the increase in the number of correct answers scored on a knowledge questionnaire and in an attitudes test administered before and after the above interventions. The secondary outcome recorded will be the reduction in BMI percentile among children deemed overweight/obese prior to the interventions. The required sample size (number of children) was calculated for a comparison of proportions with an α of 0.05 and a ß of 0.20, assuming that the Group MC subjects would show values for the measured variables at least 10% higher than those recorded for the subjects of Group HB. Corrections were made for the design effect and assuming a loss to follow-up of 10%. The maximum sample size required will be 2107 children. Data will be analysed using summary measurements for each cluster, both for making estimates and for hypothesis testing. All analyses will be made on an intention-to-treat basis. DISCUSSION: The intervention providing the best results could be recommended as part of health education for young schoolchildren. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01418872.

Sustained-release isosorbide mononitrate as adjuvant treatment in isolated systolic hypertension in the elderly.

Hypertension is one of the main cardiovascular risk factors. In the elderly, the most common form is isolated systolic hypertension, a consequence of the increase in arterial stiffness. None of the antihypertensives currently used affects arterial stiffness, whereas nitrates seem to have an effect. The aim of this work was to assess their effect on elderly patients with uncontrolled isolated systolic hypertension, defined as systolic blood pressure over 140 mmHg and diastolic blood pressure under 90 mmHg. The present study is a phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial, conducted at the University Hospital La Princesa in Madrid. Patients of both sexes, aged 65 years or older, with poorly controlled isolated systolic hypertension, were treated with 40-60 mg of sustained-release isosorbide mononitrate or matching placebo for 12 weeks. The main objective was to assess the effect on clinical pulse pressure (PP); in addition, its effect on vascular function was evaluated. Analysis was performed by intention to treat. The study was registered at the European Union Clinical Trials Register (EUDRACT 2012-002988-10) and was funded by the Spanish Ministry of Health. A total of 58 patients with an average age of 77 years were enrolled, 32 were treated with nitrate, and 26 with placebo. No significant differences were found either in PP decline (5.28 vs 7.49 mmHg, p = 0.79) or in other variables, including parameters of vascular function. There were no differences in adverse events. The results of this study have not confirmed the benefit of nitrate treatment in isolated systolic hypertension or the improvement of vascular function.

Role of telemedicine in the management of oral anticoagulation in atrial fibrillation: a practical clinical approach.

Compared with face-to-face consultations, telemedicine has many advantages, including more efficient use of healthcare resources, partial relief of the burden of care, reduced exposure to COVID-19, treatment adjustment, organization of more efficient healthcare circuits and patient empowerment. Ensuring optimal anticoagulation in atrial fibrillation patients is mandatory if we want to reduce the thromboembolic risk. Of note, telemedicine is an excellent option for the long-term management of atrial fibrillation patients. Moreover, direct oral anticoagulants may provide an added value in telemedicine (versus vitamin K antagonists), as it is not necessary to monitor anticoagulant effect or make continuous dosage adjustments. In this multidisciplinary consensus document, the role of telemedicine in anticoagulation of this population is discussed and practical recommendations are provided.

A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis.

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying conditions.

Information and consensus document for the detection and management of chronic kidney disease.

Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific associations, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals.

OBJECTIVES: A decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with serious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), but there is no knowledge of their potential role of the recovery in these patients' prognosis. This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. DESIGN: This work was a retrospective, multicentre cohort study of 9644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicine's SEMI-COVID-19 Registry. SETTING: This study examined patients hospitalised in 147 hospitals throughout Spain. PARTICIPANTS: This work analysed 9644 patients (57.12% male) out of a cohort of 12,826 patients ≥18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020. MAIN OUTCOME MEASURES: The main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death, and then multivariate analysis was carried out to control for potential confounders. RESULTS: An increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs. 22.6% in non-recoverers, OR 0.234; 95% CI, 0.154 to 0.354) and lower complication rates, especially regarding the development of acute respiratory distress syndrome (8% vs. 20.1%, p = 0.000) and ICU admission (5.4% vs. 10.8%, p = 0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor. CONCLUSION: Eosinophil recovery in patients with COVID-19 who required hospitalisation had an independent prognostic value for all-cause mortality and a milder course.