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The COVID–19 pandemic has created unprecedented challenges for health care systems globally. This study aimed to explore the presence of mental illness in a Spanish cohort of COVID-19-infected population and to evaluate the association between the presence of specific mental health conditions and the risk of death and hospitalization. This is a retrospective cohort study including all individuals with confirmed infection by SARS-CoV-2 from the PRECOVID (Prediction in COVID–19) Study (Aragon, Spain). Mental health illness was defined as the presence of schizophrenia and other psychotic disorders, anxiety, cognitive disorders, depression and mood disorders, substance abuse, and personality and eating disorders. Multivariable logistic regression models were used to examine the likelihood of 30-day all-cause mortality and COVID–19 related hospitalization based on baseline demographic and clinical variables, including the presence of specific mental conditions, by gender. We included 144,957 individuals with confirmed COVID–19 from the PRECOVID Study (Aragon, Spain). The most frequent diagnosis in this cohort was anxiety. However, some differences were observed by sex: substance abuse, personality disorders and schizophrenia were more frequently diagnosed in men, while eating disorders, depression and mood, anxiety and cognitive disorders were more common among women. The presence of mental illness, specifically schizophrenia spectrum and cognitive disorders in men, and depression and mood disorders, substance abuse, anxiety and cognitive and personality disorders in women, increased the risk of mortality or hospitalization after COVID–19, in addition to other well-known risk factors such as age, morbidity and treatment burden. Identifying vulnerable patient profiles at risk of serious outcomes after COVID–19 based on their mental health status will be crucial to improve their access to the healthcare system and the establishment of public health prevention measures for future outbreaks. [ABSTRACT FROM AUTHOR]

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=1086948) 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. [ABSTRACT FROM AUTHOR]

The disease management of long‐term breast cancer survivors (BCS) is hampered by the scarce knowledge of multimorbidity patterns. The aim of our study was to identify multimorbidity clusters among long‐term BCS and assess their impact on mortality and health services use. We conducted a retrospective study using electronic health records of 6512 BCS from Spain surviving at least 5 years. Hierarchical cluster analysis was used to identify groups of similar patients based on their chronic diagnoses, which were assessed using the Clinical Classifications Software. As a result, multimorbidity clusters were obtained, clinically defined and named according to the comorbidities with higher observed/expected prevalence ratios. Multivariable Cox and negative binomial regression models were fitted to estimate overall mortality risk and probability of contacting health services according to the clusters identified. 83.7% of BCS presented multimorbidity, essential hypertension (34.5%) and obesity and other metabolic disorders (27.4%) being the most prevalent chronic diseases at the beginning of follow‐up. Five multimorbidity clusters were identified: C1‐unspecific (29.9%), C2‐metabolic and neurodegenerative (28.3%), C3‐anxiety and fractures (9.7%), C4‐musculoskeletal and cardiovascular (9.6%) and C5‐thyroid disorders (5.3%). All clusters except C5‐thyroid disorders were associated with higher mortality compared to BCS without comorbidities. The risk of mortality in C4 was increased by 64% (adjusted hazard ratio 1.64, 95% confidence interval 1.52‐2.07). Stratified analysis showed an increased risk of death among BCS with 5 to 10 years of survival in all clusters. These results help to identify subgroups of long‐term BCS with specific needs and mortality risks and to guide BCS clinical practice regarding multimorbidity. [ABSTRACT FROM AUTHOR]

Background: Clinical outcomes among COVID-19 patients vary greatly with age and underlying comorbidities. We aimed to determine the demographic and clinical factors, particularly baseline chronic conditions, associated with an increased risk of severity in COVID-19 patients from a population-based perspective and using data from electronic health records (EHR). Methods: Retrospective, observational study in an open cohort analyzing all 68,913 individuals (mean age 44.4 years, 53.2% women) with SARS-CoV-2 infection between 15 June and 19 December 2020 using exhaustive electronic health registries. Patients were followed for 30 days from inclusion or until the date of death within that period. We performed multivariate logistic regression to analyze the association between each chronic disease and severe infection, based on hospitalization and all-cause mortality. Results: 5885 (8.5%) individuals showed severe infection and old age was the most influencing factor. Congestive heart failure (odds ratio -OR- men: 1.28, OR women: 1.39), diabetes (1.37, 1.24), chronic renal failure (1.31, 1.22) and obesity (1.21, 1.26) increased the likelihood of severe infection in both sexes. Chronic skin ulcers (1.32), acute cerebrovascular disease (1.34), chronic obstructive pulmonary disease (1.21), urinary incontinence (1.17) and neoplasms (1.26) in men, and infertility (1.87), obstructive sleep apnea (1.43), hepatic steatosis (1.43), rheumatoid arthritis (1.39) and menstrual disorders (1.18) in women were also associated with more severe outcomes. Conclusions: Age and specific cardiovascular and metabolic diseases increased the risk of severe SARS-CoV-2 infections in men and women, whereas the effects of certain comorbidities are sex specific. Future studies in different settings are encouraged to analyze which profiles of chronic patients are at higher risk of poor prognosis and should therefore be the targets of prevention and shielding strategies. [ABSTRACT FROM AUTHOR]

Background: There is little verified information on global healthcare utilization by irregular migrants. Understanding how immigrants use healthcare services based on their needs is crucial to establish effective health policy. We compared healthcare utilization between irregular migrants, documented migrants, and Spanish nationals in a Spanish autonomous community. Methods: This retrospective, observational study included the total adult population of Aragon, Spain: 930,131 Spanish nationals; 123,432 documented migrants; and 17,152 irregular migrants. Healthcare utilization data were compared between irregular migrants, documented migrants and Spanish nationals for the year 2011. Multivariable standard or zero-inflated negative binomial regression models were generated, adjusting for age, sex, length of stay, and morbidity burden. Results: The average annual use of healthcare services was lower for irregular migrants than for documented migrants and Spanish nationals at all levels of care analyzed: primary care (0.5 vs 4 vs 6.7 visits); specialized care (0.2 vs 1.8 vs 2.9 visits); planned hospital admissions (0.3 vs 2 vs 4.23 per 100 individuals), unplanned hospital admissions (0.5 vs 3.5 vs 5.2 per 100 individuals), and emergency room visits (0.4 vs 2.8 vs 2.8 per 10 individuals). The average annual prescription drug expenditure was also lower for irregular migrants (€9) than for documented migrants (€77) and Spanish nationals (€367). These differences were only partially attenuated after adjusting for age, sex, and morbidity burden. Conclusions: Under conditions of equal access, healthcare utilization is much lower among irregular migrants than Spanish nationals (and lower than that of documented migrants), regardless of country of origin or length of stay in Spain. [ABSTRACT FROM AUTHOR]

Background: There is little verified information on the global health status of undocumented migrants (UMs). Our aim is to compare the prevalence of the main chronic diseases and of multimorbidity in undocumented migrants, documented migrants, and Spanish nationals in a Spanish autonomous community. Methods: Retrospective observational study of all users of the public health system of the region of Aragon over 1 year (2011): 930,131 Spanish nationals; 123,432 documented migrants (DMs); and 17,152 UMs. Binary logistic regression was performed to examine the association between migrant status (Spanish nationals versus DMs and UMs) and both multimorbidity and individual chronic diseases, adjusting for age and sex. Results: The prevalence of individual chronic diseases in UMs was lower than in DMs and much lower than in Spanish nationals. Comparison with the corresponding group of Spanish nationals revealed odds ratios (OR) of 0.1–0.3 and 0.3–0.5 for male and female UMs, respectively (p < 0.05 in all cases). The risk of multimorbidity was lower for UMs than DMs, both for men (OR, 0.12; 95%CI 0.11–0.13 versus OR, 0.53; 95%CI 0.51–0.54) and women (OR, 0.18; 95%CI 0.16–0.20 versus OR, 0.74; 95%CI 0.72–0.75). Conclusions: Analysis of data from a health system that offers universal coverage to all immigrants, irrespective of legal status, reveals that the prevalence of chronic disease and multimorbidity is lower in UMs as compared with both DMs and Spanish nationals. These findings refute previous claims that the morbidity burden in UM populations is higher than that of the native population of the host country. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess how disease burden caused by chronic conditions is related to mortality (predictive validity) and other health outcomes (convergent validity). This was studied in 625 community-dwelling adults living in Spain aged 65 years and older. Disease burden was measured with the Disease Burden Morbidity Assessment (DBMA). The association with 5-year mortality was assessed using a Cox model and Kaplan–Meier curves. For convergent validity, mean age, sex ratio, patient-centered outcomes and healthcare utilization were compared for high and low DBMA scores (< 10 vs. ≥ 10). Also, a multivariable linear regression model was used to evaluate the DBMA as a function of these variables. Mean DBMA score in our sample was 7.5. After 5 years, 35 participants had died (5.5%). The Cox model displayed a hazard ratio of 1.07, and the Kaplan–Meier curves showed lower survival for high DBMA scores. Among participants with high DBMA scores, low self-perceived health, disability and female sex were more frequent, and this group showed lower mean scores for quality of life (Personal Wellbeing Index), affect balance (Scale of Positive and Negative Experience) and physical activity (Yale Physical Activity Survey), higher mean age and higher healthcare utilization than persons with low DBMA scores. In the multivariable regression, all variables but age were significantly associated with the DBMA. In conclusion, the DBMA showed satisfactory predictive and convergent validity. In our aging society, it can be applied to better understand and improve care for older persons with multiple chronic conditions. [ABSTRACT FROM AUTHOR]

Background: Although acute bronchitis is frequently viral in nature, antibiotics are usually inappropriately prescribed in Primary Care to treat this condition, with serious public health consequences.Objective: To determine the prevalence and predictors of appropriate management of antibiotic use in acute bronchitis processes diagnosed in outpatients in the Spanish region of Aragón.Methods: Four different electronic health databases provided demographic and clinical information pertaining to patients diagnosed with acute bronchitis in Primary Care in Aragón during 2011, as well as data for corresponding antibiotic prescriptions dispensed at pharmacies. We evaluated adherence to recommendations for antibiotic use in acute bronchitis episodes in adults collected in both international and national guidelines. Finally, regression analyses were used to identify factors associated with appropriate antibiotic management.Results: A total of 54701 episodes of acute bronchitis were registered, 9.5% of which corresponded to patients with an underlying chronic respiratory disease. In adults, antibiotics were prescribed in 64.9% of episodes, 17.9% of which involved prescription of a first-choice agent. Overall, 48.5% of episodes were appropriately managed according to guidelines. The likelihood of appropriate treatment was higher for female patients, and lower for patients who were older, presented chronic co-morbidities or were using corticoids.Conclusions: We observed poor levels of adherence to recommendations for antibiotic prescribing in adults with acute bronchitis, in terms of both the decision to prescribe and the choice of antibiotic agent. Older acute bronchitis patients and those with co-morbidities were at greater risk of being inappropriately treated. [ABSTRACT FROM AUTHOR]

Background: The healthcare of immigrants is an important aspect of equity of care provision. Understanding how immigrants use the healthcare services based on their needs is crucial to establish effective health policy.Methods: This retrospective, observational study included the total population of Aragon, Spain (1,251,540 individuals, of whom 11.9 % were immigrants). Patient-level data on the use of primary, specialised, hospital, and emergency care as well as prescription drug use in 2011 were extracted from the EpiChron Cohort and compared between immigrants and nationals. Multivariable standard or zero-inflated negative binomial regression models were generated, adjusting for age, sex, length of stay, and morbidity burden.Results: The annual visit rates of immigrants were lower than those of nationals for primary care (3.3 vs 6.4), specialised care (1.3 vs 2.7), planned hospital admissions/100 individuals (1.6 vs 3.8), unplanned hospital admissions/100 individuals (2.7 vs 4.7), and emergency room visits/10 individuals (2.3 vs 2.8). Annual prescription drug costs were also lower for immigrants (€47 vs €318). These differences were only partially attenuated after adjusting for age, sex and morbidity burden.Conclusion: In a universal coverage health system offering broad legal access to immigrants, the global use of healthcare services was lower for immigrants than for nationals. These differences may be explained in part by the healthy migration effect, but also reveal possible inequalities in healthcare provision that warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Although equity in health care is theoretically a cornerstone in Western societies, several studies show that services do not always provide equitable care for immigrants. Differences in pharmaceutical consumption between immigrants and natives are explained by variances in predisposing factors, enabling factors and needs across populations, and can be used as a proxy of disparities in health care use. By comparing the relative differences in pharmacological use between natives and immigrants from the same four countries of origin living in Spain and Norway respectively, this article presents a new approach to the study of inequity in health care. Methods: All purchased drug prescriptions classified according to the Anatomical Therapeutic Chemical (ATC) system in Aragon (Spain) and Norway for a total of 5 million natives and nearly 100,000 immigrants for one calendar year were included in this cross-sectional study. Age and gender adjusted relative purchase rates for immigrants from Poland, China, Colombia and Morocco compared to native populations in each of the host countries were calculated. Direct standardisation was performed based on the 2009 population structure of the OECD countries. Results: Overall, a significantly lower proportion of immigrants in Aragon (Spain) and Norway purchased pharmacological drugs compared to natives. Patterns of use across the different immigrant groups were consistent in both host countries, despite potential disparities between the Spanish and Norwegian health care systems. Immigrants from Morocco showed the highest drug use rates in relation to natives, especially for antidepressants, "pain killers" and drugs for peptic ulcer. Immigrants from China and Poland showed the lowest use rates, while Colombians where more similar to host countries. Conclusions: The similarities found between the two European countries in relation to immigrants' pharmaceutical use disregarding their host country emphasises the need to consider specific immigrant-related features when planning and providing healthcare services to this part of the population. These results somehow remove the focus on inequity as the main reason to explain differences in purchase between immigrants and natives. [ABSTRACT FROM AUTHOR]

Background Physical activity (PA) has been shown to improve the general health of patients with chronic diseases and to prevent the onset of such conditions. However, the association between multimorbidity and PA has not been investigated in detail, and recent studies of this topic yield dissenting results. The objective of this study was to examine whether PA levels were associated with multimorbidity, self-rated health and functional limitation. Methods This was a cross-sectional study based on data from the 2009 European Health Interview Survey for Spain. The sample population included 2,190 adults over 15 years of age. The independent variables were multimorbidity (measured as the number of chronic diseases), activity limitations, and self-rated health status. The dependent variable was PA level, measured as a) a continuous variable in metabolic equivalents (METs) and b) a dichotomous variable based on international recommendations (74 years), using multivariate linear and logistic regression models that were adjusted for age, educational level and employment status. Results An inverse association was found between PA and multimorbidity among older males and young females between 16-24 years. This negative association was also observed among males aged 25-44 years when analysing PA as a dichotomous variable. Self-rated health status was directly related to the achievement of minimum PA levels among middle-aged and older individuals, but the opposite happened among the youngest group of females. Significant associations between the existence of activity limitations and the performance of lower volumes of PA were consistently observed among subjects over 44 years. Conclusions There is an inverse association between multimorbidity and PA in the youngest and oldest age groups. In addition, both low self-rated health status and the presence of functional limitations were related to lower PA in most of the examined population groups. These features should be considered in the design and implementation of community-based approaches to promoting PA, if further corroborated in longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: There is evidence suggesting that the use of health services is lower among immigrants after adjusting for age and sex. This study takes a step forward to compare primary care (PC) utilisation patterns between immigrants and the native population with regard to their morbidity burden. Methods: This retrospective, observational study looked at 69,067 individuals representing the entire population assigned to three urban PC centres in the city of Zaragoza (Aragon, Spain). Poisson models were applied to determine the number of annual PC consultations per individual based on immigration status. All models were first adjusted for age and sex and then for age, sex and case mix (ACG System®). Results: The age and sex adjusted mean number of total annual consultations was lower among the immigrant population (children: IRR = 0.79, p < 0.05; adults: IRR = 0.73, p < 0.05). After adjusting for morbidity burden, this difference decreased among children (IRR = 0.94, p < 0.05) and disappeared among adults (IRR = 1.00). Further analysis considering the PC health service and type of visit revealed higher usage of routine diagnostic tests among immigrant children (IRR = 1.77, p < 0.05) and a higher usage of emergency services among the immigrant adult population (IRR = 1.2, p < 0.05) after adjusting for age, sex and case mix. Conclusions: Although immigrants make lower use of PC services than the native population after adjusting the consultation rate for age and sex, these differences decrease significantly when considering their morbidity burden. These results reinforce the 'healthy migration effect' and discount the existence of differences in PC utilisation patterns between the immigrant and native populations in Spain. [ABSTRACT FROM AUTHOR]

Background: In the financing of a national health system, where pharmaceutical spending is one of the main cost containment targets, predicting pharmacy costs for individuals and populations is essential for budget planning and care management. Although most efforts have focused on risk adjustment applying diagnostic data, the reliability of this information source has been questioned in the primary care setting. We sought to assess the usefulness of incorporating pharmacy data into claims-based predictive models (PMs). Developed primarily for the U.S. health care setting, a secondary objective was to evaluate the benefit of a local calibration in order to adapt the PMs to the Spanish health care system. Methods: The population was drawn from patients within the primary care setting of Aragon, Spain (n = 84,152). Diagnostic, medication and prior cost data were used to develop PMs based on the Johns Hopkins ACG methodology. Model performance was assessed through r-squared statistics and predictive ratios. The capacity to identify future high-cost patients was examined through c-statistic, sensitivity and specificity parameters. Results: The PMs based on pharmacy data had a higher capacity to predict future pharmacy expenses and to identify potential high-cost patients than the models based on diagnostic data alone and a capacity almost as high as that of the combined diagnosis-pharmacy-based PM. PMs provided considerably better predictions when calibrated to Spanish data. Conclusion: Understandably, pharmacy spending is more predictable using pharmacy-based risk markers compared with diagnosis-based risk markers. Pharmacy-based PMs can assist plan administrators and medical directors in planning the health budget and identifying high-cost-risk patients amenable to care management programs. [ABSTRACT FROM AUTHOR]

Background: The computerisation of primary health care (PHC) records offers the opportunity to focus on pharmacy expenditure from the perspective of the morbidity of individuals. The objective of the present study was to analyse the behaviour of pharmacy expenditure within different morbidity groups. We paid special attention to the identification of individuals who had higher values of pharmacy expenditure than their morbidity would otherwise suggest (i.e. outliers). Methods: Observational study consisting of 75,574 patients seen at PHC centres in Zaragoza, Spain, at least once in 2005. Demographic and disease variables were analysed (ACG® 8.1), together with a response variable that we termed 'total pharmacy expenditure per patient'. Outlier patients were identified based on boxplot methods, adjusted boxplot for asymmetric distributions, and by analysing standardised residuals of tobit regression models. Results: The pharmacy expenditure of up to 7% of attendees in the studied PHC centres during one year exceeded expectations given their morbidity burden. This group of patients was responsible for up to 24% of the total annual pharmacy expenditure. There was a significantly higher number of outlier patients within the low-morbidity band which matched up with the higher variation coefficient observed in this group (3.2 vs. 2.0 and 1.3 in the moderate- and high-morbidity bands, respectively). Conclusions: With appropriate validation, the methodologies of the present study could be incorporated in the routine monitoring of the prescribing profile of general practitioners. This could not only enable evaluation of their performance, but also target groups of outlier patients and foster analyses of the causes of unusually high pharmacy expenditures among them. This interpretation of pharmacy expenditure gives new clues for the efficiency in utilisation of healthcare resources, and could be complementary to management interventions focused on individuals with a high morbidity burden. [ABSTRACT FROM AUTHOR]

This study analyses how both ambulatory care groups (ACGs) and physician characteristics explain the variability in health-service use among primary care patients in Spain. During the period 1996–1997, data derived from 52 152 patients and their 38 respective primary care physicians were collected. The response variables were as follows: number of visits; diagnostic tests requested; and referrals to a specialist. ACGs are an important variable that should be taken into account in order to explain health-service utilization. As for professionals, age and the post they hold are essential factors. Most of the unexplained variability is caused by patient characteristics. [ABSTRACT FROM AUTHOR]

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 (Aragón, 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. [ABSTRACT FROM AUTHOR]

This study aims to describe the clinical course, drug use, and health services use characteristics during the last year of life of elders who die being centenarians and to identify key aspects differentiating them from elders who die at an earlier age, with a particular focus on sex differences. We conducted an observational, population-based study in the EpiChron Cohort (Aragón, Spain). The population was stratified by sex and into three age sub-populations (80–89, 90–99, and ≥100 years), and their characteristics were described and compared. Multimorbidity was the rule in our elders, affecting up to 3 in 4 centenarians and 9 in 10 octogenarians and nonagenarians. Polypharmacy was also observed in half of the centenarian population and in most of the younger elders. Risk factors for cardiovascular disease (i.e., hypertension, dyslipidaemia, diabetes), cerebrovascular disease and dementia were amongst the most common chronic conditions in all age groups, whereas the gastroprotective drugs and antithrombotic agents were the most dispensed drugs. Centenarians presented in general lower morbidity and treatment burden and lower use of both primary and hospital healthcare services than octogenarians and nonagenarians, suggesting a better health status. Sex-differences in their clinical characteristics were more striking in octogenarians and tended to decrease with age. [ABSTRACT FROM AUTHOR]

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 (Aragón, 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. [ABSTRACT FROM AUTHOR]

Background: Mortality is a robust indicator of health and offers valuable insight into the health of immigrants. However, mortality estimates can vary significantly depending on the manner in which immigrant status is defined. Here, we assess the impact of nationality, country of origin, and length of stay in the host country on mortality estimates in an immigrant population in Aragón, Spain.Methods: Cross-sectional retrospective study of all adult subjects from the EpiChron Cohort in 2011 (n = 1,102,544), of whom 146,100 were foreign-born (i.e., according to place of birth) and 127,213 were non-nationals (i.e., according to nationality). Directly standardized death proportions between years 2012-2015 were calculated, taking into account the age distribution of the European population in 2013. Binary logistic regression was used to compare the four-year probability of death.Results: The age- and sex-standardized number of deaths per 1000 subjects were 45.1 (95%CI 44.7-45.2) for the Spanish-born population, 29.3 (95%CI 26.7-32.1) for the foreign-born population, and 18.4 (95%CI 15.6-21.6) for non-Spanish nationals. Compared with the Spanish-born population, the age- and sex-adjusted likelihood of dying was equally reduced in the foreign-born and non-national populations (OR 0.6; 95%CI 0.5-0.7) when the length of stay was less than 10 years. No significant differences in mortality estimates were detected when the length of stay was over 10 years.Conclusions: Mortality estimates in immigrant populations were lower than those of the native Spanish population, regardless of the criteria applied. However, the proportion of deaths was lower when immigrant status was defined using nationality instead of country of birth. Age- and sex-standardized death proportions tended to increase with increased length of stay in the host country. [ABSTRACT FROM AUTHOR]

Background: The consequences of multimorbidity include polypharmacy and repeated referrals for specialised care, which may increase the risk of adverse drug events (ADEs).Aim: The objective of this study was to analyse the influence of multimorbidity, polypharmacy, and multiple referrals on the frequency of ADEs, as an indicator of therapeutic safety, in the context of a national healthcare system.Design and Setting: This was a multicentre, retrospective, observational study of 79 089 adult patients treated during 2008 in primary care centres.Method: The explanatory patient variables sex, age, level of multimorbidity, polypharmacy, number of primary care physician visits, and number of different specialties attended were analysed. The response variable was the occurrence of ADEs. Logistic regression models were used to identify associations among the analysed variables.Results: The prevalence of individuals with at least one ADE was 0.88%. Multivariate analysis identified the following variables as risk factors for the occurrence of ADE in descending order of effect size: multimorbidity level (odds ratio [OR]Veryhigh/Low = 45.26; ORHigh/Low = 17.58; ORModerate/Low = 4.25), polypharmacy (OR = 1.34), female sex (OR = 1.31), number of different specialties (OR = 1.20), and number of primary care physician visits (OR = 1.01). Age, however, did not show statistical significance (OR = 1.00; 95% confidence interval = 0.996 to 1.005).Conclusion: The results of this study demonstrate that multimorbidity is strongly related to the occurrence of ADEs, insofar as it requires the intervention of multiple specialties and the prescription of multiple medications. Further research should shed light on the causal pathway between multimorbidity and increased risk of adverse events. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe patterns of use and characteristics of 10 commonly used antidepressants for the period 2009-2014 in Denmark, Germany, Spain, and Sweden.Methods: Adult initiators from 2009 to 2014 of each study antidepressant were identified in four countries using five data sources: the Danish National registers, GePaRD (Germany), EpiChron (Aragon, Spain), SIDIAP (Catalonia, Spain), and the Swedish National Registers. The study included 10 study antidepressants: citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, mirtazapine, and agomelatine.Results: Citalopram was the most prescribed study antidepressant, followed by mirtazapine. Paroxetine and agomelatine were the least prescribed antidepressants. Mirtazapine was widely used among older antidepressant initiators with higher percentages of comorbidities at baseline, and fluoxetine was used among young patients. Citalopram and amitriptyline had the lowest percentage of multiple antidepressant use in the 12 months prior to the current treatment episode, while agomelatine, duloxetine, and venlafaxine had the highest percentage of multiple antidepressant use in the year prior to the current treatment episode.Limitations: The most important limitations are exposure information based on filled prescriptions, focus on antidepressant initiators only, lack of information on the indication, and heterogeneity of the type of data across data sources.Conclusions: Results of this study including 4.8 million study antidepressant initiators of study antidepressants suggest that citalopram and mirtazapine are the most commonly prescribed antidepressants. Agomelatine and paroxetine were the least used antidepressants in the participating populations. Mirtazapine was the antidepressant most commonly prescribed among older antidepressant initiators with high percentage of comorbidities at baseline, whereas fluoxetine was commonly used among young patients. [ABSTRACT FROM AUTHOR]

Introduction: The presence of multiple chronic conditions, also referred to as multimorbidity, is a common finding in adults. Epidemiologic research can help identify groups of individuals with similar clinical profiles who could benefit from similar interventions. Many cross-sectional studies have revealed the existence of different multimorbidity patterns. Most of these studies were focused on the older population. However, multimorbidity patterns begin to form at a young age and can evolve over time following distinct multimorbidity trajectories with different impact on health. In this study, we aimed to identify multimorbidity patterns and trajectories in adults 18-65 years old., Methods: We conducted a retrospective longitudinal epidemiologic study in the EpiChron Cohort, which includes all inhabitants of Aragón (Spain) registered as users of the Spanish National Health System, linking, at the patient level, information from electronic health records from both primary and specialised care. We included all 293,923 patients 18-65 years old with multimorbidity in 2011. We used cluster analysis at baseline (2011) and in 2015 and 2019 to identify multimorbidity patterns at four and eight years of follow-up, and we then created alluvial plots to visualise multimorbidity trajectories. We performed age- and sex-adjusted logistic regression analysis to study the association of each pattern with four- and eight-year mortality., Results: We identified three multimorbidity patterns at baseline, named dyslipidaemia & endocrine-metabolic , hypertension & obesity , and unspecific . The hypertension & obesity pattern, found in one out of every four patients was associated with a higher likelihood of four- and eight-year mortality (age- and sex-adjusted odds ratio 1.11 and 1.16, respectively) compared to the unspecific pattern. Baseline patterns evolved into different patterns during the follow-up., Discussion: Well-known preventable cardiovascular risk factors were key elements in most patterns, highlighting the role of hypertension and obesity as risk factors for higher mortality. Two out of every three patients had a cardiovascular profile with chronic conditions like diabetes and obesity that are linked to low-grade systemic chronic inflammation. More studies are encouraged to better characterise the relatively large portion of the population with an unspecific disease pattern and to help design and implement effective and comprehensive strategies towards healthier ageing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ioakeim-Skoufa, González-Rubio, Aza-Pascual-Salcedo, Laguna-Berna, Poblador-Plou, Vicente-Romero, Coelho, Santos-Mejías, Prados-Torres, Moreno-Juste and Gimeno-Miguel.)

A major risk factor of COVID-19 severity is the patient's health status at the time of the infection. Numerous studies focused on specific chronic diseases and identified conditions, mainly cardiovascular ones, associated with poor prognosis. However, chronic diseases tend to cluster into patterns, each with its particular repercussions on the clinical outcome of infected patients. Network analysis in our population revealed that not all cardiovascular patterns have the same risk of COVID-19 hospitalization or mortality and that this risk depends on the pattern of multimorbidity, besides age and sex. We evidenced that negative outcomes were strongly related to patterns in which diabetes and obesity stood out in older women and men, respectively. In younger adults, anxiety was another disease that increased the risk of severity, most notably when combined with menstrual disorders in women or atopic dermatitis in men. These results have relevant implications for organizational, preventive, and clinical actions to help meet the needs of COVID-19 patients., (© 2022. The Author(s).)

This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice.

The pressing problem of multimorbidity and polypharmacy is aggravated by the lack of specific care models for this population. We aimed to investigate the evolution of multimorbidity and polypharmacy patterns in a given population over a 4-year period (2011-2015). A cross-sectional, observational study among the EpiChron Cohort, including anonymized demographic, clinical and drug dispensation information of all users of the public health system ≥65 years in Aragon (Spain), was performed. An exploratory factor analysis, stratified by age and sex, using an open cohort was carried out based on the tetra-choric correlations among chronic diseases and dispensed drugs during 2011 and compared with 2015. Seven baseline patterns were identified during 2011 named as: mental health, respiratory, allergic, mechanical pain, cardiometabolic, osteometabolic, and allergic/derma. Of the epidemiological patterns identified in 2015, six were already present in 2011 but a new allergic/derma one appeared. Patterns identified in 2011 were more complex in terms of both disease and drugs. Results confirmed the existing association between age and clinical complexity. The systematic associations between diseases and drugs remain similar regarding their clinical nature over time, helping in early identification of potential interactions in multimorbid patients with a high risk of negative health outcomes due to polypharmacy.

Chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis, and obstructive sleep apnea (OSA) are amongst the most common treatable and preventable chronic conditions with high morbidity burden and mortality risk. We aimed to explore the existence of multimorbidity clusters in patients with such diseases and to estimate their prevalence and impact on mortality. We conducted an observational retrospective study in the EpiChron Cohort (Aragon, Spain), selecting all patients with a diagnosis of allergic rhinitis, asthma, COPD, and/or OSA. The study population was stratified by age (i.e., 15-44, 45-64, and ≥ 65 years) and gender. We performed cluster analysis, including all chronic conditions recorded in primary care electronic health records and hospital discharge reports. More than 75% of the patients had multimorbidity (co-existence of two or more chronic conditions). We identified associations of dermatologic diseases with musculoskeletal disorders and anxiety, cardiometabolic diseases with mental health problems, and substance use disorders with neurologic diseases and neoplasms, amongst others. The number and complexity of the multimorbidity clusters increased with age in both genders. The cluster with the highest likelihood of mortality was identified in men aged 45 to 64 years and included associations between substance use disorder, neurologic conditions, and cancer. Large-scale epidemiological studies like ours could be useful when planning healthcare interventions targeting patients with chronic obstructive airway diseases and multimorbidity.

Patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD) constitute a complex population with different phenotypes based on pathophysiology, comorbidity, sex and age. We aimed to compare the multimorbidity patterns of HF and COPD in men and women using network analysis. Individuals aged 40 years or older on 2015 of the EpiChron Cohort (Aragon, Spain) were stratified by sex and as having COPD (n = 28,608), HF (n = 13,414), or COPD and HF (n = 3952). We constructed one network per group by obtaining age-adjusted phi correlations between comorbidities. For each sex, networks differed between the three study groups; between sexes, similarities were found for the two HF groups. We detected some specific diseases highly connected in all networks (e.g., cardio-metabolic, respiratory diseases, and chronic kidney failure), and some others that were group-specific that would require further study. We identified common clusters (i.e., cardio-metabolic, cardiovascular, cancer, and neuro-psychiatric) and others specific and clinically relevant in COPD patients (e.g., behavioral risk disorders were systematically associated with psychiatric diseases in women and cancer in men). Network analysis represents a powerful tool to analyze, visualize, and compare the multimorbidity patterns of COPD and HF, also facilitated by developing an ad hoc website., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus (T2D) is often accompanied by chronic diseases, including mental health problems. We aimed at studying mental health comorbidity prevalence in T2D patients and its association with T2D outcomes through a retrospective, observational study of individuals of the EpiChron Cohort (Aragón, Spain) with prevalent T2D in 2011 (n = 63,365). Participants were categorized as having or not mental health comorbidity (i.e., depression, anxiety, schizophrenia, and/or substance use disorder). We performed logistic regression models, controlled for age, sex and comorbidities, to analyse the likelihood of 4-year mortality, 1-year all-cause hospitalization, T2D-hospitalization, and emergency room visit. Mental health comorbidity was observed in 19% of patients. Depression was the most frequent condition, especially in women (20.7% vs. 7.57%). Mortality risk was higher in patients with mental health comorbidity (odds ratio 1.24; 95% confidence interval 1.16-1.31), especially in those with substance use disorder (2.18; 1.84-2.57) and schizophrenia (1.82; 1.50-2.21). Mental health comorbidity also increased the likelihood of all-cause hospitalization (1.16; 1.10-1.23), T2D-hospitalization (1.51; 1.18-1.93) and emergency room visit (1.26; 1.21-1.32). These results suggest that T2D healthcare management should include specific strategies for the early detection and treatment of mental health problems to reduce its impact on health outcomes.

Purpose: To determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for hip fracture and identify other factors associated with hip fracture., Patients and Methods: Observational nested case-control study was conducted in Aragon, Spain in 2010. We included COPD patients aged >40 years, in the EpiChron cohort. Each COPD patient was matched for age, sex, and number of comorbidities with a control subject without COPD. Patients with an existing diagnosis of osteoporosis and those with hip fracture before 2011 were excluded. We collected baseline demographic, comorbidity, and pharmacological treatment data. During a 5-year follow-up period, we recorded the incidence of hip fracture. A logistic regression model was constructed to identify factors associated with hip fracture., Results: The study population consisted of 26,517 COPD patients and the same number of controls (median [interquartile range] age, 74 [17] years; women, 24.7%). Smoking and heart failure were more frequent in COPD patients, and obesity, hypertension, diabetes, dyslipidemia, stroke, arthritis, and visual or hearing impairment were less frequent (all p<0.001). Consumption of benzodiazepines (p=0.037), bronchodilators (p<0.001), and corticosteroids (p<0.001) was higher in the COPD group, while that of beta-blockers and thiazides was lower (both p<0.001). During follow-up, 898 (1.7%) patients experienced hip fracture, with no differences observed between COPD and control patients. Multivariate analysis revealed that independent of COPD status, age, female sex, chronic liver disease, heart failure, and benzodiazepine use were independently associated with a higher risk of hip fracture, and obesity with a lower risk. In COPD patients, use of inhaled anticholinergics was independently associated with hip fracture (OR, 1.390; 95% CI 1.134-1.702; p=0.001)., Conclusion: COPD is not a risk factor for a hip fracture within 5 years. The association between the use of inhaled anticholinergics and risk of hip fracture warrants further study., Competing Interests: Jesús Díez-Manglano reports grants from Fondo de Investigaciones Sanitarias ISCIII, REDISSEC, and European Regional Development Fund, during the conduct of the study. The authors report no other potential conflicts of interest for this work., (© 2020 Díez-Manglano et al.)

Background: Multimorbidity is a global health challenge that is associated with polypharmacy, increasing the risk of potentially inappropriate prescribing (PIP). There are tools to improve prescription, such as implicit and explicit criteria., Objective: To estimate the prevalence of PIP in a population aged 65 to 74 years with multimorbidity and polypharmacy, according to American Geriatrics Society Beers Criteria® (2015, 2019), the Screening Tool of Older Person's Prescription -STOPP- criteria (2008, 2014), and the Medication Appropriateness Index -MAI- criteria in primary care., Methods: This was an observational, descriptive, cross-sectional study. The sample included 593 community-dwelling elderly aged 65 to 74 years, with multimorbidity and polypharmacy, who participated in the MULTIPAP trial. Socio-demographic, clinical, professional, and pharmacological-treatment variables were recorded. Potentially inappropriate prescribing was detected by computerized prescription assistance system, and family doctors evaluated the MAI. The MAI-associated factors were analysed using a logistic regression model., Results: A total of 4,386 prescriptions were evaluated. The mean number of drugs was 7.4 (2.4 SD). A total of 94.1% of the patients in the study had at least one criterion for drug inappropriateness according to the MAI. Potentially inappropriate prescribing was detected in 57.7%, 43.6%, 68.8% and 71% of 50 patients according to the explicit criteria STOPP 2014, STOPP 2008, Beers 2019 and Beers 2015 respectively. For every new drug taken by a patient, the MAI score increased by 2.41 (95% CI 1.46; 3.35) points. Diabetes, ischaemic heart disease and asthma were independently associated with lower summated MAI scores., Conclusions: The prevalence of potentially inappropriate prescribing detected in the sample was high and in agreement with previous literature for populations with multimorbidity and polypharmacy. The MAI criteria detected greater inappropriateness than did the explicit criteria, but their application was more complex and difficult to automate., Competing Interests: The authors have declared that no competing interests exist.

Multimorbidity, the coexistence of several chronic conditions in a patient, represents a great challenge for healthcare systems and society. The Integrated Multimorbidity Care Model (IMCM) was recently designed within the Joint Action on chronic diseases and promoting healthy ageing across the life cycle (CHRODIS) to ensure the continuity of care for patients with multimorbidity. The IMCM was implemented in five European pilot sites in Spain, Italy, and Lithuania, within the Joint Action CHRODIS-PLUS. The effect of these pilot interventions was assessed pre- and post-implementation by 17 healthcare managers, using the Assessment of Chronic Illness Care (ACIC) measure, and by 226 patients with the Patient Assessment of Care for Chronic Conditions (PACIC+) survey. The ACIC total score significantly increased (5.23 to 6.71, p = 0.022) after the intervention, with differences across sites. A significant increase in the PACIC+ summary score was found ranging from 3.25 at baseline to 4.03 after the intervention ( p < 0.001), and 58% of the sample perceived an improvement in care. Higher PACIC+ scores after the intervention were associated to lower baseline values in the respective PACIC+ dimension and to greater changes in ACIC Part 1 (delivery system organization). The IMCM implementation can help improve the quality of care for patients with multimorbidity.

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.

The correct management of patients with multimorbidity remains one of the main challenges for healthcare systems worldwide. In this study, we analyze the existence of multimorbidity patterns in the general population based on gender and age. We conducted a cross-sectional study of individuals of all ages from the EpiChron Cohort, Spain (1,253,292 subjects), and analyzed the presence of systematic associations among chronic disease diagnoses using exploratory factor analysis. We identified and clinically described a total of 14 different multimorbidity patterns (12 in women and 12 in men), with some relevant differences in the functions of age and gender. The number and complexity of the patterns was shown to increase with age in both genders. We identified associations of circulatory diseases with respiratory disorders, chronic musculoskeletal diseases with depression and anxiety, and a very consistent pattern of conditions whose co-occurrence is known as metabolic syndrome (hypertension, diabetes, obesity, and dyslipidaemia), among others. Our results demonstrate the potential of using real-world data to conduct large-scale epidemiological studies to assess the complex interactions among chronic conditions. This could be useful in designing clinical interventions for patients with multimorbidity, as well as recommendations for healthcare professionals on how to handle these types of patients in clinical practice.

The World Health Organization considers the non-adherence to medication a significant issue with global impact, especially in chronic conditions such as type 2 diabetes. We aim to study antidiabetic treatment initiation, add-on, treatment switching, and medication persistence. We conducted an observational study on 4247 individuals initiating antidiabetic treatment between 2013 and 2014 in the EpiChron Cohort (Spain). We used Cox regression models to estimate the likelihood of non-persistence after a one-year follow-up, expressed as hazard ratios (HRs). Metformin was the most frequently used first-line antidiabetic (80% of cases); combination treatment was the second most common treatment in adults aged 40-79 years, while dipeptidyl peptidase-4 inhibitors were the second most common in individuals in their 80s and over, and in patients with renal disease. Individuals initiated on metformin were less likely to present addition and switching events compared with any other antidiabetic. Almost 70% of individuals initiated on monotherapy were persistent. Subjects aged 40 and over (HR 0.53-0.63), living in rural (HR 0.79) or more deprived areas (HR 0.77-0.82), or receiving polypharmacy (HR 0.84), were less likely to show discontinuation. Our findings could help identify the population at risk of discontinuation, and offer them closer monitoring for proper integrated management to improve prognosis and health outcomes.

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings.

Background and Objective: Sub-optimal adherence to treatment in the general population has been highlighted in several studies, especially in the elderly and/or chronic patients. This study aims to describe the adherence to treatment of diabetes mellitus, dyslipidaemia and hypertension, and to identify the factors that influence adherence., Material and Method: Retrospective, cross-sectional observational study on 16,208 patients aged ≥65 years from the EpiChron Cohort who initiated monotherapy treatment of an antidiabetic, a lipid-lowering or an antihypertensive medication in 2010. Adherence was measured by calculating the medication possession ratio during one year, considering those cases with medication possession ratio ≥80% to be adherent. We performed a descriptive study, and a logistic regression model was used to identify the predictors of low adherence., Results: Adherence to antidiabetics, antihypertensive and lipid-lowering drugs was 72.4%, 50.7% and 44.3%, respectively. An increase in adherence of 3-8% was observed for each additional chronic disease suffered by the patient. The presence of mental illness did not affect adherence, and sex, age and number of prescribed drugs did not present consistent effects., Conclusion: The results obtained show a sub-optimal adherence to treatment for the 3chronic diseases studied. Adherence increased with the number of chronic diseases, while sex, age and number of drugs did not show a consistent effect. It is necessary to investigate if there are other factors that may influence therapeutic adherence, since improving adherence may have a greater impact on health than any progress in therapies., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

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., (© 2019 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.)

Objectives: The objective was to identify the systematic associations among chronic diseases and drugs in the form of patterns and to describe and clinically interpret the constituted patterns with a focus on exploring the existence of potential drug-drug and drug-disease interactions and prescribing cascades., Methods: This observational, cross-sectional study used the demographic and clinical information from electronic medical databases and the pharmacy billing records of all users of the public health system of the Spanish region of Aragon in 2015. An exploratory factor analysis was conducted based on the tetra-choric correlations among the diagnoses of chronic diseases and the dispensed drugs in 887,572 patients aged ≤65 years. The analysis was stratified by age and sex. To name the constituted patterns, assess their clinical nature, and identify potential interactions among diseases and drugs, the associations found in each pattern were independently reviewed by two pharmacists and two doctors and tested against the literature and the information reported in the technical medicinal forms., Results: Six multimorbidity-polypharmacy patterns were found in this large-scale population study, named as respiratory, mental health, cardiometabolic, endocrinological, osteometabolic, and mechanical-pain. The nature of the patterns in terms of diseases and drugs differed by sex and age and became more complex as age advanced., Conclusions: The six clinically sound multimorbidity-polypharmacy patterns described in this non-elderly population confirmed the existence of systematic associations among chronic diseases and medications, and revealed some unexpected associations suggesting the prescribing cascade phenomenon as a potential underlying factor. These findings may help to broaden the focus and orient the early identification of potential interactions when caring for multimorbid patients at high risk of adverse health outcomes due to polypharmacy., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of the study is to evaluate the effectiveness of risk minimization measures-labeling changes and communication to health care professionals-recommended by the European Medicines Agency for use of cilostazol for the treatment of intermittent claudication in Europe., Methods: Observational study of cilostazol in The Health Improvement Network (United Kingdom), EpiChron Cohort (Spain), SIDIAP (Spain), Swedish National Databases, and GePaRD (Germany). Among new users of cilostazol, we compared the prevalence of conditions targeted by the risk minimization measures in the periods before (2002-2012) and after (2014) implementation. Conditions evaluated were prevalence of smoking, cardiovascular conditions, concurrent use of ≥2 antiplatelet agents, concurrent use of potent CYP3A4/CYP2C19 inhibitors and high-dose cilostazol, early monitoring of all users, and continuous monitoring of users at high cardiovascular risk., Results: We included 22 593 and 1821 new users of cilostazol before and after implementation of risk minimization measures, respectively. After implementation, the frequency of several conditions related to the labeling changes improved in all the study populations: prevalence of use decreased between 13% (EpiChron) and 57% (SIDIAP), frequency of cardiovascular contraindications decreased between 8% (GePaRD) and 84% (EpiChron), and concurrent use of high-dose cilostazol and potent CYP3A4/CYP2C19 inhibitors decreased between 6% (Sweden) and 100% (EpiChron). The frequency of other conditions improved in most study populations, except smoking, which decreased only in EpiChron (48% reduction)., Conclusions: This study indicates that the risk minimization measures implemented by the EMA for the use of cilostazol have been effective in all European countries studied, except for smoking cessation before initiating cilostazol, which remains an area of improvement., (© 2018 The Authors. Pharmacoepidemiology & Drug Safety published by John Wiley & Sons Ltd.)

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 12 months, 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 65-74 years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3 months)., 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, NCT02866799.

Background/objectives: The clinical status of older individuals with multimorbidity can be further complicated by concomitant geriatric syndromes. This study explores multimorbidity patterns, encompassing both chronic diseases and geriatric syndromes, in geriatric patients attended in an acute hospital setting., Design: Retrospective observational study., Setting: Unit of Social and Clinical Assessment (UVSS), Miguel Servet University Hospital (HUMS), Zaragoza (Spain). Year, 2011., Participants: A total of 924 hospitalized patients aged 65 years or older., Measurements: Data on patients' clinical, functional, cognitive and social statuses were gathered through comprehensive geriatric assessments. To identify diseases and/or geriatric syndromes that cluster into patterns, an exploratory factor analysis was applied, stratifying by sex. The factors can be interpreted as multimorbidity patterns, i.e., diseases non-randomly associated with each other within the study population. The resulting patterns were clinically assessed by several physicians., Results: The mean age of the study population was 82.1 years (SD 7.2). Multimorbidity burden was lower in men under 80 years, but increased in those over 80. Immobility, urinary incontinence, hypertension, falls, dementia, cognitive decline, diabetes and arrhythmia were among the 10 most frequent health problems in both sexes, with prevalence rates above 20%. Four multimorbidity patterns were identified that were present in both sexes: Cardiovascular, Induced Dependency, Falls and Osteoarticular. The number of conditions comprising these patterns was similar in men and women., Conclusion: The existence of specific multimorbidity patterns in geriatric patients, such as the Induced Dependency and Falls patterns, may facilitate the early detection of vulnerability to stressors, thus helping to avoid negative health outcomes such as functional disability.

Background: As the population ages, the prevalence of multimorbidity also increases, with consequences to several health outcomes such as disability and quality of life (QoL). This study aimed at analyzing the relationships between chronic conditions, disability, and QoL of older adults with multimorbidity in Spain., Method: Data on older adults aged 65 years or more, with at least two chronic health conditions were drawn from three cohort studies. Sample size was 705, 443, and 4995, respectively. For each cohort, the impact of the following chronic health conditions was analyzed: asthma, cancer, cardiac, diabetes, hypertension, mental health disorders, osteoarticular conditions, and stroke. Disability and QoL measures varied according to the survey., Results: In older adults with multimorbidity, the most prevalent conditions were osteoarticular (59.08-67.80%) and hypertension (50.64-60.03%). The presence of disability was significantly associated to having osteoarticular (OR range: 1.53 to 2.646), diabetes (OR: 1.86 to 1.71), or mental health disorders (OR: 2.19 to 3.36) in most cohorts. Disability (OR: 1.67 to 7.67), osteoarticular conditions (OR: 3.37 to 5.10), and mental health disorders (OR: 1.83 to 4.27) showed the highest effects on lower QoL than the population., Conclusion: The presence of disability and diverse chronic conditions has a negative effect on QoL of older adults affected by multimorbidity in Spain. Public health and primary care interventions focusing on the integrated care of older adults with multimorbidity might give special attention to mental health and osteoarticular conditions., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To analyse the association between cardiovascular and mental comorbidities of obesity and weight loss registered in the electronic primary healthcare records., Design and Setting: Longitudinal study of a cohort of adult patients assigned to any of the public primary care centres in Aragon, Spain, during 2010 and 2011., Participants: Adult obese patients for whom data on their weight were available for 2010 (n=62,901), and for both 2010 and 2011 (n=42,428)., Outcomes: Weight loss (yes/no) was calculated based on the weight difference between the first value registered in 2010 and the last value registered in 2011. Multivariate logistic regression models were adjusted for individuals' age, sex, total number of chronic comorbidities, type of obesity and length of time between both weight measurements., Results: According to the recorded clinical information, 9 of 10 obese patients showed at least one chronic comorbidity. After adjusting for covariates, weight loss seemed to be more likely among obese patients with a diagnosis of diabetes and/or dementia and less likely among those with hypertension, anxiety and/or substance use problems (p<0.05). The probability of weight loss was also significantly higher in male patients with more severe obesity and older age., Conclusions: An increased probability of weight loss over 1 year was observed in older obese male patients, especially among those already manifesting high levels of obesity and severe comorbidities such as diabetes and/or dementia. Yet patients with certain psychological problems showed lower rates of weight reduction. Future research should clarify if these differences persist beyond potential selective weight documentation in primary care, to better understand the trends in weight reduction among obese patients and the underlying role of general practitioners regarding such trends., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To compare the similarities among the multimorbidity patterns identified in primary care patients from two European regions (Spain and the Netherlands) with similar organisational features of their primary care systems, using validated methodologies., Methodology: This observational, retrospective, multicentre study analysed information from primary care electronic medical records. Multimorbidity patterns were assessed using exploratory factor analysis of the diagnostic information of patients over 14 years of age. The analysis was stratified by age groups and sex., Results: The analysis of Dutch data revealed a higher prevalence of multimorbidity which corresponds with the clustering of a higher number of diseases in each of the patterns. Relevant clinical similarities were found between both countries for three multimorbidity patterns that were previously identified in the original Spanish study: cardiometabolic, mechanical and psychiatric-substance abuse. In addition, the clinical evolution towards complexity of the cardiometabolic pattern with advancing age--already demonstrated in the original study--was corroborated in the Dutch context. A clear association between mechanical and psychosocial disorders was unique to the Dutch population, as well as the recurrent presentation of the psychiatric-substance abuse pattern in all age and sex groups., Conclusions: The similarities found for the cardiometabolic, mechanical and psychiatric-substance abuse patterns in primary care patients from two different European countries could offer initial clues for the elaboration of clinical practice guidelines, if further evidenced in other contexts. This study also endorses the use of primary care electronic medical records for the epidemiologic characterization of multimorbidity.

Background: The coexistence of several chronic diseases in one same individual, known as multimorbidity, is an important challenge facing health care systems in developed countries. Recent studies have revealed the existence of multimorbidity patterns clustering systematically associated distinct clinical entities. We sought to describe age and gender differences in the prevalence and patterns of multimorbidity in men and women over 65 years., Methods: Observational retrospective multicentre study based on diagnostic information gathered from electronic medical records of 19 primary care centres in Aragon and Catalonia. Multimorbidity patterns were identified through exploratory factor analysis. We performed a descriptive analysis of previously obtained patterns (i.e. cardiometabolic (CM), mechanical (MEC) and psychogeriatric (PG)) and the diseases included in the patterns stratifying by sex and age group., Results: 67.5% of the aged population suffered two or more chronic diseases. 32.2% of men and 45.3% of women were assigned to at least one specific pattern of multimorbidity, and 4.6% of men and 8% of women presented more than one pattern simultaneously. Among women over 65 years the most frequent pattern was the MEC pattern (33.3%), whereas among men it was the CM pattern (21.2%). While the prevalence of the CM and MEC patterns decreased with age, the PG pattern showed a higher prevalence in the older age groups., Conclusions: Significant gender differences were observed in the prevalence of multimorbidity patterns, women showing a higher prevalence of the MEC and PG patterns, as well as a higher degree of pattern overlapping, probably due to a higher life expectancy and/or worse health. Future studies on multimorbidity patterns should take into account these differences and, therefore, the study of multimorbidity and its impact should be stratified by age and sex.

Objective: To compare the prevalence of disease and drug consumption obtained by using the National Health Survey (NHS) with the information provided by the electronic medical records (EMR) in primary health care and the Pharmaceutical Consumption Registry in Aragon (Farmasalud) in the adult population in the province of Zaragoza., Methods: A cross-sectional study was performed to compare the prevalence of diseases in the NHS-2006 and in the EMR. The prevalence of drug consumption was obtained from the NHS-2006 and Farmasalud. Estimations using each database were compared with their 95% confidence intervals (95% CI) and the results were stratified by gender and age groups. The comparability of the databases was tested., Results: According to the NHS, a total of 81.8% of the adults in the province of Zaragoza visited a physician in 2006. According to the EMR, 61.4% of adults visited a primary care physician. The most prevalent disease in both databases was hypertension (NHS: 21.5%, 95% CI: 19.4-23.9; EMR: 21.6%, 95% CI: 21.3-21.8). The greatest differences between the NHS and EMR was observed in the prevalence of depression, anxiety, and other mental illnesses (NHS: 10.9%; EMR: 26.6%). The most widely consumed drugs were analgesics The prevalence of drug consumption differed in the two databases, with the greatest differences being found in pain medication (NHS: 23.3%; Farmasalud: 63.8%) and antibiotics (NHS: 3.4%; Farmasalud: 41.7%). These differences persisted after we stratified by gender and were especially important in the group aged more than 75 years., Conclusions: The prevalence of morbidity and drug consumption differed depending on the database employed. The use of different databases is recommended to estimate real prevalences., (Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.)

Objectives: The aim of this study was to demonstrate the existence of systematic associations in drug prescription that lead to the establishment of patterns of polypharmacy, and the clinical interpretation of the associations found in each pattern., Methods: A cross-sectional study was conducted based on information obtained from electronic medical records and the primary care pharmacy database in 2008. An exploratory factor analysis of drug dispensing information regarding 79,089 adult patients was performed to identify the patterns of polypharmacy. The analysis was stratified by age and sex., Results: Seven patterns of polypharmacy were identified, which may be classified depending on the type of disease they are intended to treat: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. Some of these patterns revealed a clear clinical consistency and included drugs that are prescribed together for the same clinical indication (i.e., ARI and COPD patterns). Other patterns were more complex but also clinically consistent: in the cardiovascular pattern, drugs for the treatment of known risk factors-such as hypertension or dyslipidemia-were combined with other medications for the treatment of diabetes or established cardiovascular pathology (e.g., antiplatelet agents). Almost all of the patterns included drugs for preventing or treating potential side effects of other drugs in the same pattern., Conclusions: The present study demonstrated the existence of non-random associations in drug prescription, resulting in patterns of polypharmacy that are sound from the pharmacological and clinical viewpoints and that exist in a significant proportion of the population. This finding necessitates future longitudinal studies to confirm some of the proposed causal associations. The information discovered would further the development and/or adaptation of clinical patient guidelines to patients with multimorbidity who are taking multiple drugs.