[Impact of COVID-19 on the mental health of the population: Study in primary care]. / Impacto de la COVID-19 en la salud mental de la población: estudio en atención primaria.

OBJECTIVE: To determine the prevalence of COVID-19 and the characteristics of infected patients, as well as the prevalence of mental disorders associated with the infection and the associated risk factors. Secondary: to know the prevalence of the long COVID syndrome and the characteristics of this cohort. DESIGN: Incidence study of mental disorder in patients diagnosed with COVID-19 and case-control study of long COVID syndrome in the subsample of patients diagnosed with COVID-19 without a history of mental disorder. SITE: Primary care setting in Lleida. PARTICIPANTS: The 46,258 patients diagnosed of COVID-19 without a history of mental disorder were followed for 2 years. MAIN MEASUREMENTS: The dependent variable was the mental disorder in the period 03/11/2020 to 03/11/2022; and the independent variables were clinical and social variables. Its association with mental disorder was analyzed by calculating the adjusted hazard ratio using a logistic regression model. RESULTS: The average age of 46,258 patients at the beginning of the study was 43±17.9 years. 47% were women. The mental disorder rate for all period was 3.46% (59.20% anxiety). A predictive score was elaborated. The long COVID syndrome was more common in older women, without toxic habits, with obesity and associated comorbidity. CONCLUSIONS: COVID-19 has had an impact on the mental health of patients. Knowing the risk factors for developing these mental disorders and the long COVID syndrome would allow the clinician to be able to identify patients at risk in order to establish preventive measures and avoid their appearance.

Multimorbidity patterns and 18-year transitions from normal cognition to dementia and death: A population-based study.

BACKGROUND: Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across the cognitive continuum. OBJECTIVES: We aimed to investigate the impact of multimorbidity and of specific multimorbidity patterns on the transitions across cognitive stages (normal cognition, cognitive impairment, no dementia [CIND], dementia) and death. METHODS: We included 3122 dementia-free individuals from the Swedish National study on Aging and Care in Kungsholmen. Using fuzzy c-means cluster analysis, multimorbid participants were classified into mutually exclusive groups characterized by commonly coexisting chronic diseases. Participants were followed up to 18 years to detect incident CIND, dementia, or death. Transition hazard ratios (HRs), life expectancies, and time spent in different cognitive stages were estimated using multistate Markov models. RESULTS: At baseline, five multimorbidity patterns were identified: neuropsychiatric, cardiovascular, sensory impairment/cancer, respiratory/metabolic/musculoskeletal, and unspecific. Compared to the unspecific pattern, the neuropsychiatric and sensory impairment/cancer ones showed reduced hazards of reverting from CIND to normal cognition (HR 0.53, 95% CI 0.33-0.85 and HR 0.60, 95% CI 0.39-0.91). Participants in the cardiovascular pattern exhibited an increased hazard of progression from CIND to dementia (HR 1.70, 95% CI 1.15-2.52) and for all transitions to death. Subjects with the neuropsychiatric and cardiovascular patterns showed reduced life expectancy at age 75, with an anticipation of CIND (up to 1.6 and 2.2 years, respectively) and dementia onset (up to 1.8 and 3.3 years, respectively). CONCLUSIONS: Multimorbidity patterns differentially steer individual trajectories across the cognitive continuum of older adults and may be used as a risk stratification tool.

Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study.

BACKGROUND: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. METHODS: We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. FINDINGS: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. INTERPRETATION: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. FUNDING: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).

Validation of an electronic frailty index with electronic health records: eFRAGICAP index.

OBJECTIVE: To create an electronic frailty index (eFRAGICAP) using electronic health records (EHR) in Catalunya (Spain) and assess its predictive validity with a two-year follow-up of the outcomes: homecare need, institutionalization and mortality in the elderly. Additionally, to assess its concurrent validity compared to other standardized measures: the Clinical Frailty Scale (CFS) and the Risk Instrument for Screening in the Community (RISC). METHODS: The eFRAGICAP was based on the electronic frailty index (eFI) developed in United Kingdom, and includes 36 deficits identified through clinical diagnoses, prescriptions, physical examinations, and questionnaires registered in the EHR of primary health care centres (PHC). All subjects > 65 assigned to a PHC in Barcelona on 1st January, 2016 were included. Subjects were classified according to their eFRAGICAP index as: fit, mild, moderate or severe frailty. Predictive validity was assessed comparing results with the following outcomes: institutionalization, homecare need, and mortality at 24 months. Concurrent validation of the eFRAGICAP was performed with a sample of subjects (n = 333) drawn from the global cohort and the CFS and RISC. Discrimination and calibration measures for the outcomes of institutionalization, homecare need, and mortality and frailty scales were calculated. RESULTS: 253,684 subjects had their eFRAGICAP index calculated. Mean age was 76.3 years (59.5% women). Of these, 41.1% were classified as fit, and 32.2% as presenting mild, 18.7% moderate, and 7.9% severe frailty. The mean age of the subjects included in the validation subsample (n = 333) was 79.9 years (57.7% women). Of these, 12.6% were classified as fit, and 31.5% presented mild, 39.6% moderate, and 16.2% severe frailty. Regarding the outcome analyses, the eFRAGICAP was good in the detection of subjects who were institutionalized, required homecare assistance, or died at 24 months (c-statistic of 0.841, 0.853, and 0.803, respectively). eFRAGICAP was also good in the detection of frail subjects compared to the CFS (AUC 0.821) and the RISC (AUC 0.848). CONCLUSION: The eFRAGICAP has a good discriminative capacity to identify frail subjects compared to other frailty scales and predictive outcomes.

The Immune Response in Nonmetastatic Axillary Lymph Nodes Is Associated with the Presence of Axillary Metastasis and Breast Cancer Patient Outcome.

Tumor cells can modify the immune response in primary tumors and in the axillary lymph nodes with metastasis (ALN+) in breast cancer (BC), influencing patient outcome. We investigated whether patterns of immune cells in the primary tumor and in the axillary lymph nodes without metastasis (ALN-) differed between patients diagnosed without ALN+ (diagnosed-ALN-) and with ALN+ (diagnosed-ALN+) and the implications for clinical outcome. Eleven immune markers were studied using immunohistochemistry, tissue microarray, and digital image analysis in 141 BC patient samples (75 diagnosed-ALN+ and 66 diagnosed-ALN-). Two logistic regression models were derived to identify the clinical, pathologic, and immunologic variables associated with the presence of ALN+ at diagnosis. There are immune patterns in the ALN- associated with the presence of ALN+ at diagnosis. The regression models revealed a small subgroup of diagnosed-ALN+ with ALN- immune patterns that were more similar to those of the ALN- of the diagnosed-ALN-. This small subgroup also showed similar clinical behavior to that of the diagnosed-ALN-. Another small subgroup of diagnosed-ALN- with ALN- immune patterns was found whose members were more similar to those of the ALN- of the diagnosed-ALN+. This small subgroup had similar clinical behavior to the diagnosed-ALN+. These data suggest that the immune response present in ALN- at diagnosis could influence the clinical outcome of BC patients.

Medication-related problems in older people in Catalonia: A real-world data study.

PURPOSE: The aim of this study was to determine medication-related problems (MRPs) in primary care patients over 65 years of age. METHODS: Cross-sectional study based on the electronic health records of patients (65-99 years of age) visited in 284 primary health care centers during 2012 in Catalonia. VARIABLES: age, sex, sociodemographic variables, number of drugs, kidney and liver function and MRPs (duplicate therapy, drug-drug interactions, potentially inappropriate medications [PIMs] and drugs contraindicated in chronic kidney disease and in liver diseases). Unconditional logistic regression models were used to identify the factors associated with MRPs in patients with multimorbidity. RESULTS: 916 619 older people were included and 853 085 of them met the criteria for multimorbidity. Median age was 75 years and 57.7% of them were women. High percentages of MRPs were observed: PIMs (62.8%), contraindicated drugs in chronic kidney disease (12.1%), duplicate therapy (11.1%), contraindicated drugs in liver diseases (4.2%), and drug-drug interactions (1.0%). These numbers were higher in the subgroup of patients with ≥10 diseases. The most common PIMs were connected to drugs that increase the risk of fall (66.8%), antiulcer agents without criteria for gastroprotection (40.6%), and the combination of drugs with anticholinergic effects (39.7%). In the multivariate analysis, the variables associated with all MRPs among the patients with multimorbidity were the number of drugs and the number of visits. CONCLUSIONS: The coexistence of multimorbidity and polypharmacy is associated with an elevated risk of MRPs in older people. Medication safety for older patients constitutes a pressing concern for health services.

Multimorbidity patterns and risk of frailty in older community-dwelling adults: a population-based cohort study.

BACKGROUND: the aim of this study was to examine the cross-sectional and longitudinal associations of different multimorbidity patterns with physical frailty in older adults. METHODS: we used data from the Swedish National study on Aging and Care in Kungsholmen to generate a physical frailty measure, and clusters of participants with similar multimorbidity patterns were identified through fuzzy c-means cluster analyses. The cross-sectional association (n = 2,534) between multimorbidity clusters and physical frailty was measured through logistic regression analyses. Six- (n = 2,122) and 12-year (n = 2,140) longitudinal associations were determined through multinomial logistic regression analyses. RESULTS: six multimorbidity patterns were identified at baseline: psychiatric diseases; cardiovascular diseases, anaemia and dementia; sensory impairments and cancer; metabolic and sleep disorders; musculoskeletal, respiratory and gastrointestinal diseases; and an unspecific pattern lacking any overrepresented diseases. Cross-sectionally, each pattern was associated with physical frailty compared with the unspecific pattern. Over 6 years, the psychiatric diseases (relative risk ratio [RRR]: 3.04; 95% confidence intervals [CI]: 1.59-5.79); cardiovascular diseases, anaemia and dementia (RRR 2.25; 95% CI: 1.13-4.49) and metabolic and sleep disorders (RRR 1.99; 95% CI: 1.25-3.16) patterns were associated with incident physical frailty. The cardiovascular diseases, anaemia and dementia (RRR: 4.81; 95% CI: 1.59-14.60); psychiatric diseases (RRR 2.62; 95% CI: 1.45-4.72) and sensory impairments and cancer (RRR 1.87; 95% CI: 1.05-3.35) patterns were more associated with physical frailty, compared with the unspecific pattern, over 12 years. CONCLUSIONS: we found that older adults with multimorbidity characterised by cardiovascular and neuropsychiatric disease patterns are most susceptible to developing physical frailty.

Patterns of multimorbidity and risk of disability in community-dwelling older persons.

The aim was to analyze the association between specific patterns of multimorbidity and risk of disability in older persons. Data were gathered from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); 2066 60 + year-old participants living in the community and free from disability at baseline were grouped according to their multimorbidity patterns and followed-up for six years. The association between multimorbidity patterns and disability in basic (ADL) and instrumental (IADL) activities of daily living was examined through multinomial models. Throughout the follow-up, 434 (21.0%) participants developed at least one ADL and 310 (15.0%) at least one IADL. Compared to the unspecific pattern, which included diseases not exceeding their expected prevalence in the total sample, belonging to the cardiovascular/anemia/dementia, the sensory impairment/cancer and the musculoskeletal/respiratory/gastrointestinal patterns was associated with a higher risk of developing both ADL and IADL, whereas subjects in the metabolic/sleep disorders pattern showed a higher risk of developing only IADL. Multimorbidity patterns are differentially associated with incident disability, which is important for the design of future prevention strategies aimed at delaying functional impairment in old age, and for a better healthcare resource planning.

Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics.

INTRODUCTION: We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype. METHODS: A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses. RESULTS: People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity. DISCUSSION: Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.

Multimorbidity patterns, polypharmacy and their association with liver and kidney abnormalities in people over 65 years of age: a longitudinal study.

BACKGROUND: The implementation of individual clinical practice guidelines in patients with multimorbidity often results in polypharmacy. Our aim was to analyse medication use according to longitudinal multimorbidity patterns (MP) and determine during a 5-year period (2012-16) which MP are associated with abnormal liver and kidney function in primary care patients over 65 years of age living in Catalonia. METHODS: Design: Longitudinal study (years 2012 to 2016) based on the electronic health records contained in Information System for Research in Primary Care database of the Catalan Institute of Health (SIDIAP). VARIABLES: age, sex, MP, medication and polypharmacy (drug exposure obtained from the Pharmacy Invoice Registry). Medicines were classified in accordance with the Anatomical Therapeutic Chemical Classification System (ATC). Glomerular filtration rate was used to determine abnormal kidney function, and serum levels of alkaline phosphatase, alanine transaminase and gamma-glutamyl transpeptidase were used to diagnose abnormal liver function. STATISTICS: For medication use in MP, we calculated annual mean packages of each drug in each MP, and observed/expected ratios were obtained by dividing mean packages in the cluster by mean packages of the same drug in the overall population. Logistic regression models were fitted to estimate the association between MP at baseline and abnormal kidney and liver function tests during follow up. RESULTS: Nine hundred sixteen thousand six hundred nineteen patients were included, and 743,827 completed the follow up. We identified one polypharmacy profile per MP, and concluded that the most prescribed drugs in each pattern corresponded to the diseases overrepresented in that specific MP. The median of drugs ranged from 3 (Cluster 1 - Non-Specific) to 8 (Cluster 10 - Multisystem Pattern). Abnormal kidney function was most commonly observed in the Cluster 4 - Cardio-Circulatory and Renal (Odds Ratio [OR] 2.19; Confidence interval [CI] 95% 2.15-2.23) and Cluster 3 - Minority Metabolic Autoimmune-Inflammatory (OR 2.16; CI 95% 2.12-2.20) MP. A higher risk of abnormal liver function was observed in the Cluster 8 - Digestive (OR 3.39; CI 95% 3.30-3.49), and Cluster 4 - Cardio-Circulatory and Renal (OR 1.96; CI 95% 1.91-2.02) MP. CONCLUSIONS: A higher risk of abnormal kidney and liver function was observed in specific MP. The long-term characterisation of MP and polypharmacy illustrates the burden of chronic multimorbidity and polypharmacy in the elderly population.

[Effectiveness, safety and costs of stroke prevention in non-valvular auricular fibrillation. Study of cohorts matched by Propensity score]. / Efectividad, seguridad y costes de la prevención tromboembólica en fibrilación auricular. Estudio de cohortes apareado por Propensity score.

OBJECTIVE: To analyze the use, effectiveness, safety and costs of stroke prevention in non-valvular atrial fibrillation (AF) in patients initiating treatment with dabigatran or vitamin K antagonists (VKA). SETTING: Primary Care (PC) at the Catalan Health Institute (ICS) in Catalonia, during 2011-2013. PARTICIPANTS: Patients attended in ICS PC centres with a registered diagnosis of AF who initiate dabigatran or VKA. INTERVENTIONS: Not applicable MAIN MEASUREMENTS: Number of prescriptions and reimbursements of dabigatran and VKA, incidence of stroke and haemorrhages, incidence of mortatlity, number of sickness leave, and costs associated to all the previous variables. RESULTS: 14,930 patients were included; 94.6% initiated VKA and 5.4%, dabigatran. Dabigatran patients were younger and with less comorbidity. There were no statistically significant differences between VKA and dabigatran in the risk of stroke, haemorrhages or death. The costs associated to AF management were higher for PC visits in the VKA group, and higher for laboratory and pharmacy in the dabigatran group, although overall costs were not statistically different. CONCLUSIONS: Most patients initiated VKA. We found no differences between VKA and dabigatran in the risk of stroke, haemorrhages or mortality.

Medication patterns in older adults with multimorbidity: a cluster analysis of primary care patients.

BACKGROUND: Older adults suffer from various chronic conditions which make them particularly vulnerable. The proper management of multiple drug use is therefore crucial. The aim of our study was to describe drug prescription and medication patterns in this population. METHODS: A cross-sectional study in Barcelona (Spain) using electronic health records from 50 primary healthcare centres. Participants were aged 65 to 94 years, presenting multimorbidity (≥2 chronic diseases), and had been prescribed at least 1 drug for 6 months or longer during 2009. We calculated the prevalence of prescribed drugs and identified medication patterns using multiple correspondence analysis and k-means clustering. Analyses were stratified by sex and age (65-79, 80-94 years). RESULTS: We studied 164,513 patients (66.8% women) prescribed a median of 4 drugs (interquartile range [IQR] = 3-7) in the 65-79 age-group and 6 drugs (IQR = 4-8) in the 80-94 age-group. A minimum of 45.9% of patients aged 65-79 years, and 61.8% of those aged 80-94 years, were prescribed 5 or more drugs. We identified 6 medication patterns, a non-specific one and 5 encompassing 8 anatomical groups (alimentary tract and metabolism, blood, cardiovascular, dermatological, musculo-skeletal, neurological, respiratory, and sensory organ). CONCLUSIONS: Drug prescription is widespread among the elderly. Six medication patterns were identified, 5 of which were related to one or more anatomical group, with associations among drugs from different systems. Overall, guidelines do not accurately reflect the situation of the elderly multimorbid, new strategies for managing multiple drug uses are needed to optimize prescribing in these patients.

Effectiveness of risk minimization measures for the use of cilostazol in United Kingdom, Spain, Sweden, and Germany.

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.

Multimorbidity patterns in the elderly: a prospective cohort study with cluster analysis.

BACKGROUND: Multimorbidity is the coexistence of more than two chronic diseases in the same individual; however, there is no consensus about the best definition. In addition, few studies have described the variability of multimorbidity patterns over time. The aim of this study was to identify multimorbidity patterns and their variability over a 6-year period in patients older than 65 years attended in primary health care. METHODS: A cohort study with yearly cross-sectional analysis of electronic health records from 50 primary health care centres in Barcelona. Selected patients had multimorbidity and were 65 years of age or older in 2009. Diagnoses (International Classification of Primary Care, second edition) were extracted using O'Halloran criteria for chronic diseases. Multimorbidity patterns were identified using two steps: 1) multiple correspondence analysis and 2) k-means clustering. Analysis was stratified by sex and age group (65-79 and ≥80 years) at the beginning of the study period. RESULTS: Analysis of 2009 electronic health records from 190,108 patients with multimorbidity (59.8% women) found a mean age of 71.8 for the 65-79 age group and 84.16 years for those over 80 (Standard Deviation [SD] 4.35 and 3.46, respectively); the median number of chronic diseases was seven (Interquartil range [IQR] 5-10). We obtained 6 clusters of multimorbidity patterns (1 nonspecific and 5 specifics) in each group, being the specific ones: Musculoskeletal, Endocrine-metabolic, Digestive/Digestive-respiratory, Neurological, and Cardiovascular patterns. A minimum of 42.5% of the sample remained in the same pattern at the end of the study, reflecting the stability of these patterns. CONCLUSIONS: This study identified six multimorbidity patterns per each group, one nonnspecific pattern and five of them with a specific pattern related to an organic system. The multimorbidity patterns obtained had similar characteristics throughout the study period. These data are useful to improve clinical management of each specific subgroup of patients showing a particular multimorbidity pattern.

Multimorbidity patterns with K-means nonhierarchical cluster analysis.

BACKGROUND: The purpose of this study was to ascertain multimorbidity patterns using a non-hierarchical cluster analysis in adult primary patients with multimorbidity attended in primary care centers in Catalonia. METHODS: Cross-sectional study using electronic health records from 523,656 patients, aged 45-64 years in 274 primary health care teams in 2010 in Catalonia, Spain. Data were provided by the Information System for the Development of Research in Primary Care (SIDIAP), a population database. Diagnoses were extracted using 241 blocks of diseases (International Classification of Diseases, version 10). Multimorbidity patterns were identified using two steps: 1) multiple correspondence analysis and 2) k-means clustering. Analysis was stratified by sex. RESULTS: The 408,994 patients who met multimorbidity criteria were included in the analysis (mean age, 54.2 years [Standard deviation, SD: 5.8], 53.3% women). Six multimorbidity patterns were obtained for each sex; the three most prevalent included 68% of the women and 66% of the men, respectively. The top cluster included coincident diseases in both men and women: Metabolic disorders, Hypertensive diseases, Mental and behavioural disorders due to psychoactive substance use, Other dorsopathies, and Other soft tissue disorders. CONCLUSION: Non-hierarchical cluster analysis identified multimorbidity patterns consistent with clinical practice, identifying phenotypic subgroups of patients.

Dabigatran and vitamin K antagonists' use in naïve patients with non-valvular atrial fibrillation: a cross-sectional study of primary care-based electronic health records.

PURPOSE: The purpose of this study was to characterize the profile of patients with non-valvular atrial fibrillation who start an anticoagulant treatment after diagnosis with dabigatran and compare it with those who start with vitamin K antagonists (VKAs). METHODS: We analysed primary health care-based electronic health records data from 15,075 people with new diagnosis of atrial fibrillation who initiated treatment with dabigatran or VKA spanning 2011-2013. Logistic regression analysis for determination of factors associated with initiation of dabigatran was performed. RESULTS: We identified 14,266 (94.6%) people who initiated VKA and 809 (5.4%) who initiated dabigatran. Mean age of people treated with dabigatran was lower than in VKA patients (73.7 vs 75.5 years, p < 0.001). People (90.5%) in VKA group and 83.6% in the dabigatran group had a high risk of stroke, according to CHA2DS2VASc score. There was higher proportion of people with hypertension, diabetes mellitus, dyslipidaemia, and chronic kidney disease among people treated with VKA. The proportion of people with a history of cerebral haemorrhage and stroke was higher among dabigatran patients compared with VKA patients (1.4 vs 0.6%, p = 0.015 and 14.0% vs 10.8%, p = 0.006, respectively). Multivariable logistic model showed that treatment with dabigatran was associated with male sex, history of stroke and Mortalidad en áreas pequeñas Españolas y Desigualdades Socioeconómicas index. CONCLUSIONS: Most patients recently diagnosed with non-valvular atrial fibrillation initiated treatment with VKA. Primary healthcare patients with non-valvular atrial fibrillation initiating dabigatran are younger, had a lower risk of stroke or bleeding, fewer comorbidity and more history of stroke and intracranial haemorrhage compared to those who were initiated on VKA.

Effectiveness and safety of drugs used for stroke prevention in a cohort of non-valvular atrial fibrillation patients from a primary care electronic database.

PURPOSE: The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions. METHODS: We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes. RESULTS: We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADS2 ≥ 2, HR 0.65 (95%CI, 0.49-0.86), and CHA2 DS2 -VASc ≥ 2, HR 0.66 (95%CI, 0.52-0.84). We observed a higher risk of digestive bleeding with antiplatelets, HR 1.32 (95%CI, 1.01-1.73). Both VKA and antiplatelets were associated with reduction of all-cause mortality risk; HR 0.55 (95%CI, 0.49-0.62) and HR 0.89 (95%CI, 0.80-0.97), respectively. CONCLUSIONS: This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany.

PURPOSE: To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. METHODS: New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. RESULTS: We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. CONCLUSIONS: In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events. © 2017 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

The burden of cardiovascular morbidity in a European Mediterranean population with multimorbidity: a cross-sectional study.

BACKGROUND: Cardiovascular diseases are highly represented in multimorbidity patterns. Nevertheless, few studies have analysed the burden of these diseases in the population with multimorbidity. The objective of this study was to identify and describe the cardiovascular diseases among the patients with multimorbidity. METHODS: We designed a cross-sectional study in patients ≥19 years old assigned to 251 primary health care centres in Catalonia, Spain. The main outcome was cardiovascular morbidity burden, defined as the presence of one or more of 24 chronic cardiovascular diseases in multimorbid patients (≥2 chronic conditions). Two groups were defined, with and without multimorbidity; the multimorbidity group was further divided into cardiovascular and non-cardiovascular subgroups. The secondary outcomes were: modifiable major cardiovascular risk factors (smoking, hypertension, hypercholesterolaemia, diabetes) and cardiovascular risk score (REGICOR, Registre Gironí del Cor). Other variables analysed were: sex, age (19-24, 25-44, 45-64, 65-79, and 80+ years), number of chronic diseases, urban setting, active toxic habits (smoking and alcohol), physical parameters and laboratory tests. RESULTS: A total of 1,749,710 individuals were included (mean age, 47.4 years [SD: 17.8]; 50.7 % women), of which nearly half (46.8 %) had multimorbidity (95 % CI: 46.9-47.1). In patients with multimorbidity,, the cardiovascular burden was 54.1 % of morbidity (95 % CI: 54.0-54.2) and the four most prevalent cardiovascular diseases were uncomplicated hypertension (75.3 %), varicose veins of leg (20.6 %), "other" heart disease (10.5 %) and atrial fibrillation/flutter (6.7 %). In the cardiovascular morbidity subgroup, 38.2 % had more than one cardiovascular disease. The most prevalent duet and triplet combinations were uncomplicated hypertension & lipid disorder (38.8 %) and uncomplicated hypertension & lipid disorder & non-insulin dependent diabetes (11.3 %), respectively. By age groups, the same duet was the most prevalent in patients aged 45-80 years and in men aged 25-44 years. In women aged 19-44, varicose veins of leg & anxiety disorder/anxiety was the most prevalent; in men aged 19-24, it was uncomplicated hypertension & obesity. Patients with multimorbidity showed a higher cardiovascular risk profile than the non-multimorbidity group. CONCLUSIONS: More than 50 % percent of patients with multimorbidity had cardiovascular diseases, the most frequent being hypertension. The presence of cardiovascular risk factors and the cardiovascular risk profile were higher in the multimorbidity group than the non-multimorbidity group. Hypertension, diabetes and dyslipidaemia constituted the most prevalent multimorbidity pattern.