Background: The epidemiologic study of comorbidities of an index health problem represents a methodological challenge. This study cross-sectionally describes and analyzes the comorbidities associated with dementia in older patients and reviews the existing similarities and differences between identified comorbid diseases using the statistical methods most frequently applied in current research. Methods: Cross-sectional study of 72,815 patients over 64 seen in 19 Spanish primary care centers during 2008. Chronic diseases were extracted from electronic health records and grouped into Expanded Diagnostic Clusters®. Three different statistical methods were applied (i.e., analysis of prevalence data, multiple regression and factor analysis), stratifying by sex. Results: The two most frequent comorbidities both for men and women with dementia were hypertension and diabetes. Yet, logistic regression and factor analysis demonstrated that the comorbidities significantly associated with dementia were Parkinson’s disease, congestive heart failure, cerebrovascular disease, anemia, cardiac arrhythmia, chronic skin ulcers, osteoporosis, thyroid disease, retinal disorders, prostatic hypertrophy, insomnia and anxiety and neurosis. Conclusions: The analysis of the comorbidities associated with an index disease (e.g., dementia) must not be exclusively based on prevalence rates, but rather on methodologies that allow the discovery of non-random associations between diseases. A deep and reliable knowledge about how different diseases are grouped and associated around an index disease such as dementia may orient future longitudinal studies aimed at unraveling causal associations.

We aimed to analyze baseline socio-demographic and clinical factors associated with an increased likelihood of mortality in men and women with coronavirus disease (COVID-19). We conducted a retrospective cohort study (PRECOVID Study) on all 4412 individuals with laboratory-confirmed COVID-19 in Aragon, Spain, and followed them for at least 30 days from cohort entry. We described the socio-demographic and clinical characteristics of all patients of the cohort. Age-adjusted logistic regressions models were performed to analyze the likelihood of mortality based on demographic and clinical variables. All analyses were stratified by sex. Old age, specific diseases such as diabetes, acute myocardial infarction, or congestive heart failure, and dispensation of drugs like vasodilators, antipsychotics, and potassium-sparing agents were associated with an increased likelihood of mortality. Our findings suggest that specific comorbidities, mainly of cardiovascular nature, and medications at the time of infection could explain around one quarter of the mortality in COVID-19 disease, and that women and men probably share similar but not identical risk factors. Nonetheless, the great part of mortality seems to be explained by other patient- and/or health-system-related factors. More research is needed in this field to provide the necessary evidence for the development of early identification strategies for patients at higher risk of adverse outcomes.

Background and Purpose: We aimed to determine the prevalence and predictors of delayed neurological improvement (DNI) after complete endovascular reperfusion in anterior circulation acute ischemic stroke (AIS). Methods: Retrospective analysis of an online multicenter prospective reperfusion registry of patients with consecutive anterior circulation AIS treated with endovascular thrombectomy (EVT) from January 2018 to June 2019 in tertiary stroke centers of the NORDICTUS (NORD-Spain Network for Research and Innovation in ICTUS) network. We included patients with AIS with a proximal occlusion in whom a modified Thrombolysis in Cerebral Infarction 3 reperfusion pattern was obtained. DNI was defined if, despite absence of early neurological improvement during the first 24 hours, patients achieved functional independence on day 90. Clinical and radiological variables obtained before EVT were analyzed as potential predictors of DNI. Results: Of 1565 patients with consecutive AIS treated with EVT, 1381 had proximal anterior circulation occlusions, 803 (58%) of whom achieved a modified Thrombolysis in Cerebral Infarction 3. Of these, 628 patients fulfilled all selection criteria and were included in the study. Mean age was 73.8 years, 323 (51.4%) were female, and median baseline National Institutes of Health Stroke Scale was 16. Absence of early neurological improvement was observed in 142 (22.6%) patients; 32 of these (22.5%) achieved good long-term outcome and constitute the DNI group. Predictors of DNI in multivariable-adjusted logistic regression were male sex (odds ratio, 6.4 [95% CI, 2.1–22.3] P =0.002), lower pre-EVT National Institutes of Health Stroke Scale score (odds ratio, 1.4 [95% CI, 1.2–1.5], P <0.001), and intravenous thrombolysis (odds ratio, 9.1 [95% CI, 2.7–30.90], P <0.001). Conclusions: One-quarter of patients with anterior circulation AIS who do not clinically improve within the first 24 hours after complete cerebral endovascular recanalization will achieve long-term functional independence, regardless of the poor early clinical course. Male sex, lower initial clinical severity, and use of intravenous thrombolysis before EVT predicted this clinical pattern.

In 2008, stroke mortality, morbidity, and disability rates in Aragon were higher than the average in Spain. These data underscored the need to develop a stroke care programme (PAIA). We present the dynamics of planning, implementation, evaluation, and improvement developed between 2009 and 2014 as well as the results of the PAIA after that 5-year period. Structure, processes, and outcomes have improved with reference to the key indicators of healthcare (audit: 2008, 2010, 2012) among others: stroke rate in 2013 was 2.07 (2.36 in 2008); 78% of strokes were managed in stroke units in 2014 (30% in 2008); rate of fibrinolysis was 8.3% in 2014 (4.4% in 2010); fibrinolysis was administered in secondary hospitals (30% of the total); fibrinolysis was administered by Telestroke in 9%; stroke mortality decreased (38%); 67.7 years of potential life lost (YPLL) in 2013 (144 in 2008); nurse training; development of neurosonology; networking; sharing protocols and best practices between health sectors, etc. CONCLUSIONS: Integrated process management and multidisciplinary teams distributed and deployed over an entire territory with established protocols, references, evaluations, and continuous development, have been proven powerful tools to ensure both quality and equality. The PAIA is a good example of clinical governance and networking due to its dynamic and sustained improvement and cooperation between clinicians.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84–41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.