Multimorbilidad, fragilidad y resultados en salud en población geriátrica

Antecedentes y objetivosLa multimorbilidad, definida como la presencia de dos o más enfermedades crónicas de forma simultánea en un individuo, y la fragilidad, es decir el estado de vulnerabilidad ante factores estresantes, tienen un gran impacto en la salud de los pacientes y en el uso de los recursos sanitarios. El objetivo general de esta tesis que se presenta es avanzar en el conocimiento de la epidemiología de la multimorbilidad en pacientes geriátricos y su impacto sobre los resultados en salud (interacción con la dependencia funcional, la mortalidad y la utilización de servicios sanitarios), basándonos en el análisis de grandes bases de datos clínico-administrativas de la población de Aragón. Las preguntas de investigación se responden en cuatro artículos publicados y vinculados a cada uno de los siguientes objetivos específicos: a) explorar la multimorbilidad en población geriátrica hospitalizada, b) caracterizar la población geriátrica centenaria de Aragón, c) definir las variables demográficas y clínicas que diferencian a los centenarios de los ancianos más jóvenes de Aragón y d) analizar la utilidad de la armonización de bases de datos en la caracterización de la población geriátrica con multimorbilidad y fragilidad en Europa.MetodologíaEl primer objetivo específico se abordó a través de análisis factorial exploratorio de los diagnósticos crónicos y síndromes geriátricos para la identificación de patrones de multimorbilidad, basado en correlaciones tetracóricas, debido a la naturaleza dicotómica (presencia/ausencia) de la variable diagnóstica. Análisis estratificado por grupos de edad y sexo.El segundo y tercer objetivos específicos se abordó mediante un estudio observacional retrospectivo en la Cohorte EpiChron (Aragón). Análisis de las características sociodemográficas, clínicas, consumo de fármacos y utilización de servicios sanitarios, utilizando información de historia clínica electrónica y bases de datos clínico-administrativas. Los resultados se han calculado como medias y/o frecuencias con intervalo de confianza del 95%. Para el análisis de diferencias por sexo, se ha utilizado el test de Kruskal-Wallis para comparar las medias y el test Chi-cuadrado de Pearson para comparar frecuencias. La significación estadística se ha establecido en pEl cuarto objetivo se abordó a través de un estudio descriptivo para valorar la capacidad de armonización de 4 bases de datos sobre salud en personas mayores.ConclusionesEl patrón de multimorbilidad dependencia inducida, compuesto exclusivamente por síndromes geriátricos, puede actuar como desencadenante del deterioro funcional, lo que subraya la importancia de la evaluación global de los pacientes geriátricos. La multimorbilidad parece ser la regla más que la excepción en esta población, que presenta principalmente un patrón cardiocerebrovascular. Abordar la atención médica en las personas mayores desde una perspectiva geriátrica integral es fundamental para preservar su salud y evitar los efectos negativos de la polifarmacia. El estado de salud aparentemente mejor en los centenarios que en nonagenarios y octogenarios, deja la puerta abierta para reconocer que esta población muere más como consecuencia de un mecanismo de envejecimiento biológico natural que por la presencia de enfermedades específicas. La identificación de factores potenciales para una longevidad excepcional requeriría más estudios longitudinales multidisciplinarios que deberían analizar simultáneamente información clínica, bioquímica y de estilo de vida.La aplicación de metodologías comunes de registro de información, facilita la armonización, la fusión de datos, la extrapolación a otros contextos y la posibilidad de trabajar de forma conjunta en múltiples campos de la geriatría. <br /

Sex Differences in Comorbidity, Therapy, and Health Services' Use of Heart Failure in Spain: Evidence from Real-World Data

Heart failure (HF) is becoming increasingly prevalent and affects both men and women. However, women have traditionally been underrepresented in HF clinical trials. In this study, we aimed to analyze sex differences in the comorbidity, therapy, and health services'' use of HF patients. We conducted a cross-sectional study in Aragón (Spain) and described the characteristics of 17, 516 patients with HF. Women were more frequent (57.4 vs. 42.6%, p < 0.001) and older (83 vs. 80 years, p < 0.001) than men, and presented a 33% lower risk of 1-year mortality (p < 0.001). Both sexes showed similar disease burdens, and 80% suffered six or more diseases. Some comorbidities were clearly sex-specific, such as arthritis, depression, and hypothyroidism in women, and arrhythmias, ischemic heart disease, and COPD in men. Men were more frequently anti-aggregated and anti-coagulated and received more angiotensin-converting-enzyme (ACE) inhibitors and beta-blockers, whereas women had more angiotensin II antagonists, antiinflammatories, antidepressants, and thyroid hormones dispensed. Men were admitted to specialists (79.0 vs. 70.6%, p < 0.001), hospital (47.0 vs. 38.1%, p < 0.001), and emergency services (57.6 vs. 52.7%, p < 0.001) more frequently than women. Our results highlight the need to conduct future studies to confirm the existence of these differences and of developing separate HF management guidelines for men and women that take into account their sex-specific comorbidity

Prevalence and Comorbidity of Atopic Dermatitis in Children: A Large-Scale Population Study Based on Real-World Data

This study aimed at exploring atopic dermatitis (AD) prevalence in children and exhaustively analyzing their comorbidity. We conducted a descriptive analysis of their socio-demographic and comorbidity characteristics in the EpiChron Cohort (Aragon, Spain). Adjusted odds ratios (OR) were calculated for each comorbidity using logistic regression models. In total, 33, 591 children had a diagnosis of AD, resulting in an overall prevalence of 15.5%. AD prevalence was higher in girls compared to boys, in 3-9-year-olds compared to children of other ages, and in Spanish children compared to those of other nationalities. Multimorbidity was present in 43% of children, with the most frequent chronic comorbidities being asthma (13.1%), psychosocial disorders (7.9%), and visual impairment (7.8%). Many diseases were, regardless of their prevalence, statistically associated with AD. The strongest associations (odds ratio (OR) (95% confidence interval (CI))) were found in asthma (2.10 (2.02-2.17)), allergic rhinitis (2.00 (1.91-2.10)), and irritable bowel syndrome (1.90 (1.56-2.31)). A better understanding of the array of comorbidities associated with AD in children might help improve their clinical management. Future longitudinal studies are encouraged to shed light on the potential underlying pathophysiological mechanisms involved in the identified associations

Health of Spanish centenarians: A cross-sectional study based on electronic health records

Background: With the number of centenarians increasing exponentially in Spain, a deeper knowledge of their socio-demographic, clinical, and healthcare use characteristics is important to better understand the health profile of the very elderly. Methods: We conducted a retrospective, cross-sectional observational study in the EpiChron Cohort (Aragon, Spain) aimed at analyzing the socio-demographic, clinical, drug use and healthcare use characteristics of 1680 centenarians during 2011-2015, using data from electronic health records and clinical-administrative databases. Results: Spanish centenarians (79.1% women) had 101.6 years on average. Approximately 80% of centenarians suffered from multimorbidity, with an average of 4.0 chronic conditions; 50% were exposed to polypharmacy, with an average of 4.8 medications; only 6% of centenarians were free of chronic diseases and only 7% were not on medication. Centenarians presented a cardio-cerebrovascular pattern in which hypertension, heart failure, cerebrovascular disease and dementia were the most frequent conditions. Primary care was the most frequently visited healthcare level (79% of them), followed by medical specialist consultations (23%), hospitalizations (13%), and emergency service use (9%). Conclusions: Multimorbidity is the rule rather than the exception in Spanish centenarians. Addressing medical care in the very elderly from a holistic geriatric view is critical in order to preserve their health, and avoid the negative effects of polypharmacy

Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: a study in three European data sources

This is the peer reviewed version of the following article: Forns, J. [et al.]. Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: a study in three European data sources. "Pharmacoepidemiology and drug safety", 6 Juny 2019, vol. 28, núm. 7, p. 965-975, which has been published in final form at 10.1002/pds.4803. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.&quot;Purpose Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs). Methods Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group. Results Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code “unspecified jaundice” had high PPVs in Denmark. Conclusions PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.Peer ReviewedPostprint (author's final draft

Multimorbidity, social determinants and intersectionality in chronic patients. Results from the EpiChron Cohort

Background: Multimorbidity is influenced in an interconnected way, both in extent and nature, by the social determinants of health. We aimed at implementing an intersectional approach to analyse the association of multimorbidity with five important axes of social inequality (i.e. gender, age, ethnicity, residence area and socioeconomic class). Methods: We conducted a cross-sectional observational study of all individuals who presented with at least one chronic disease in 2019 (n = 1 086 948) from the EpiChron Cohort (Aragon, Spain). Applying intersectional analysis, the age-adjusted likelihood of multimorbidity was investigated across 36 intersectional strata defined by gender, ethnicity, residence area and socioeconomic class. We calculated odds ratios (OR) 95% confidence interval (CI) using high-income urban non-migrant men as the reference category. The area under the receiver operator characteristics curve (AUC) was calculated to evaluate the discriminatory accuracy of multimorbidity. Results: The prevalence of multimorbidity increased with age, female gender and low income. Young and middle-aged low-income individuals showed rates of multimorbidity equivalent to those of high-income people aged about 20 years older. The intersectional analysis showed that low-income migrant women living in urban areas for >15 years were particularly disadvantaged in terms of multimorbidity risk OR = 3.16 (95% CI = 2.79-3.57). Being a migrant was a protective factor for multimorbidity, and newly arrived migrants had lower multimorbidity rates than those with >15 years of stay in Aragon, and even non-migrants. Living in rural vs. urban areas was slightly protective against multimorbidity. All models had a large discriminatory accuracy (AUC = 0.7884-0.7895); the largest AUC was obtained for the model including all intersectional strata. Conclusions: Our intersectional approach uncovered the large differences in the prevalence of multimorbidity that arise due to the synergies between the different socioeconomic and demographic exposures, beyond their expected additive effects

Multimorbidity patterns in patients with heart failure: an observational Spanish study based on electronic health records

Objectives To characterise the comorbidities of heart failure (HF) in men and women, to explore their clustering into multimorbidity patterns, and to measure the impact of such patterns on the risk of hospitalisation and mortality. Design Observational retrospective population study based on electronic health records. Setting EpiChron Cohort (Aragón, Spain). Participants All the primary and hospital care patients of the EpiChron Cohort with a diagnosis of HF on 1 January 2011 (ie, 8488 women and 6182 men). We analysed all the chronic diseases registered in patients’ electronic health records until 31 December 2011. Primary outcome We performed an exploratory factor analysis to identify the multimorbidity patterns in men and women, and logistic and Cox proportional-hazards regressions to investigate the association between the patterns and the risk of hospitalisation in 2012, and of 3-year mortality. Results Almost all HF patients (98%) had multimorbidity, with an average of 7.8 chronic diseases per patient. We identified six different multimorbidity patterns, named cardiovascular, neurovascular, coronary, metabolic, degenerative and respiratory. The most prevalent were the degenerative (64.0%) and cardiovascular (29.9%) patterns in women, and the metabolic (49.3%) and cardiovascular (43.2%) patterns in men. Every pattern was associated with higher hospitalisation risks; and the cardiovascular, neurovascular and respiratory patterns significantly increased the likelihood of 3-year mortality. Conclusions Multimorbidity is the norm rather than the exception in patients with heart failure, whose comorbidities tend to cluster together beyond simple chance in the form of multimorbidity patterns that have different impact on health outcomes. This knowledge could be useful to better understand common pathophysiological pathways underlying this condition and its comorbidities, and the factors influencing the prognosis of men and women with HF. Further large scale longitudinal studies are encouraged to confirm the existence of these patterns as well as their differential impact on health outcomes

Multimorbidity patterns in COVID-19 patients and their relationship with infection severity : MRisk-COVID study

Several chronic conditions have been identified as risk factors for severe COVID-19 infection, yet the implications of multimorbidity need to be explored. The objective of this study was to establish multimorbidity clusters from a cohort of COVID-19 patients and assess their relationship with infection severity/mortality. The MRisk-COVID Big Data study included 14 286 COVID-19 patients of the first wave in a Spanish region. The cohort was stratified by age and sex. Multimorbid individuals were subjected to a fuzzy c-means cluster analysis in order to identify multimorbidity clusters within each stratum. Bivariate analyses were performed to assess the relationship between severity/mortality and age, sex, and multimorbidity clusters. Severe infection was reported in 9.5% (95% CI: 9.0-9.9) of the patients, and death occurred in 3.9% (95% CI: 3.6-4.2). We identified multimorbidity clusters related to severity/mortality in most age groups from 21 to 65 years. In males, the cluster with highest percentage of severity/mortality was Heart-liver-gastrointestinal (81-90 years, 34.1% severity, 29.5% mortality). In females, the clusters with the highest percentage of severity/mortality were Diabetes-cardiovascular (81-95 years, 22.5% severity) and Psychogeriatric (81-95 years, 16.0% mortality). This study characterized several multimorbidity clusters in COVID-19 patients based on sex and age, some of which were found to be associated with higher rates of infection severity/mortality, particularly in younger individuals. Further research is encouraged to ascertain the role of specific multimorbidity patterns on infection prognosis and identify the most vulnerable morbidity profiles in the community. Registered 4 August 2021 (retrospectively registered)

Chronic obstructive pulmonary disease (COPD) as a disease of early aging: evidence from the epiChron cohort

Background: Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. Methods and findings: We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Conclusion: Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age

Applying the FAIR4Health Solution to Identify Multimorbidity Patterns and Their Association with Mortality through a Frequent Pattern Growth Association Algorithm

This article belongs to the Special Issue Addressing the Growing Burden of Chronic Diseases and Multimorbidity: Characterization and InterventionsThe current availability of electronic health records represents an excellent research opportunity on multimorbidity, one of the most relevant public health problems nowadays. However, it also poses a methodological challenge due to the current lack of tools to access, harmonize and reuse research datasets. In FAIR4Health, a European Horizon 2020 project, a workflow to implement the FAIR (findability, accessibility, interoperability and reusability) principles on health datasets was developed, as well as two tools aimed at facilitating the transformation of raw datasets into FAIR ones and the preservation of data privacy. As part of this project, we conducted a multicentric retrospective observational study to apply the aforementioned FAIR implementation workflow and tools to five European health datasets for research on multimorbidity. We applied a federated frequent pattern growth association algorithm to identify the most frequent combinations of chronic diseases and their association with mortality risk. We identified several multimorbidity patterns clinically plausible and consistent with the bibliography, some of which were strongly associated with mortality. Our results show the usefulness of the solution developed in FAIR4Health to overcome the difficulties in data management and highlight the importance of implementing a FAIR data policy to accelerate responsible health research.This study was performed in the framework of FAIR4Health, a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 824666. Also, this research has been co-supported by the Carlos III National Institute of Health, through the IMPaCT Data project (code IMP/00019), and through the Platform for Dynamization and Innovation of the Spanish National Health System industrial capacities and their effective transfer to the productive sector (code PT20/00088), both co-funded by European Regional Development Fund (FEDER) ‘A way of making Europe’, and by REDISSEC (RD16/0001/0005) and RICAPPS (RD21/0016/0019) from Carlos III National Institute of Health. This work was also supported by Instituto de Investigación Sanitaria Aragón and Carlos III National Institute of Health [Río Hortega Program, grant number CM19/00164].Peer reviewe