Multimorbidity in Incident Heart Failure: Characterisation and Impact on 1-Year Outcomes.

Background/Objectives: Heart failure (HF) is usually accompanied by other comorbidities, which, altogether, have a major impact on patients and healthcare systems. Our aim was to analyse the demographic and clinical characteristics of incident HF patients and the effect of comorbidities on one-year health outcomes. Methods: This was an observational, retrospective, population-based study of incident HF patients between 2014 and 2018 in the EpiChron Cohort, Spain. The included population contained all primary and hospital care patients with a diagnosis of HF. All chronic diseases in their electronic health records were pooled into three comorbidity clusters (cardiovascular, mental, other physical). These comorbidity groups and the health outcomes were analysed until 31 December 2018. A descriptive analysis was performed. Cox regression models and survival curves were calculated to determine the hazard risk (HR) of all-cause mortality, all-cause and HF-related hospital admissions, hospital readmissions, and emergency room visits for each comorbidity group. Results: In total, 13,062 incident HF patients were identified (mean age = 82.0 years; 54.8% women; 93.7% multimorbid; mean of 4.52 ± 2.06 chronic diseases). After one-year follow-up, there were 3316 deaths (25.3%) and 4630 all-cause hospitalisations (35.4%). After adjusting by gender, age, and inpatient/outpatient status, the mental cluster was associated (HR; 95% confidence interval) with a higher HR of death (1.08; 1.01-1.16) and all-cause hospitalisation (1.09; 1.02-1.16). Conclusions: Cardiovascular comorbidities are the most common and studied ones in HF patients; however, they are not the most strongly associated with negative impacts on health outcomes in these patients. Our findings suggest the importance of a holistic and integral approach in the care of HF patients and the need to take into account the entire spectrum of comorbidities for improving HF management in clinical practice.

Multimorbidity patterns and trajectories in young and middle-aged adults: a large-scale population-based cohort study.

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.

Mental health and risk of death and hospitalization in COVID-19 patients. Results from a large-scale population-based study in Spain.

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.

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

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

Multimorbidity Clusters in the Oldest Old: Results from the EpiChron Cohort.

Multimorbidity is challenging for both patients and healthcare systems due to its increasing prevalence and high impact on people's health and well-being. The risk of multimorbidity increases with age, but there is still more to discover regarding the clinical profile of the oldest old. In this study, we used information from the EpiChron Cohort Study to identify multimorbidity patterns in individuals who died during the period 2010-2019 at the ages of 80-89, 90-99, and ≥100. This cohort links the demographic, clinical, and drug dispensation information of public health system users in Aragón, Spain. We saw a significantly lower number of chronic diseases and drugs and a lower prevalence of polypharmacy in centenarians compared to those aged 80-99. K-means clustering revealed different multimorbidity clusters by sex and age group. We observed clusters of cardiovascular and metabolic diseases, obstructive pulmonary conditions, and neoplasms, amongst other profiles. One in three octogenarian women had a metabolic pattern (diabetes, dyslipidaemia, and other endocrine-metabolic disorders) with the highest number of diseases (up to seven) and prevalence of polypharmacy (64%). We observed clusters of dementia and genitourinary disorders in individuals on medication with anticholinergic activity. Our study offers an opportunity to better understand the urgency of adequately addressing multimorbidity in our older adults.

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

The current availability of electronic health records represents an excellent research opportunity on multimorbidity, one of the most relevant public health problems nowadays. However, it also poses a methodological challenge due to the current lack of tools to access, harmonize and reuse research datasets. In FAIR4Health, a European Horizon 2020 project, a workflow to implement the FAIR (findability, accessibility, interoperability and reusability) principles on health datasets was developed, as well as two tools aimed at facilitating the transformation of raw datasets into FAIR ones and the preservation of data privacy. As part of this project, we conducted a multicentric retrospective observational study to apply the aforementioned FAIR implementation workflow and tools to five European health datasets for research on multimorbidity. We applied a federated frequent pattern growth association algorithm to identify the most frequent combinations of chronic diseases and their association with mortality risk. We identified several multimorbidity patterns clinically plausible and consistent with the bibliography, some of which were strongly associated with mortality. Our results show the usefulness of the solution developed in FAIR4Health to overcome the difficulties in data management and highlight the importance of implementing a FAIR data policy to accelerate responsible health research.

Changes in Multimorbidity and Polypharmacy Patterns in Young and Adult Population over a 4-Year Period: A 2011-2015 Comparison Using Real-World Data.

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.

An Estimation of the Incidence of Thyroiditis Among Girls in Primary Care in Spain

Objective: As for other auto-immune processes, thyroiditis is monitored after vaccinations. The aim was to estimate the baseline incidence of thyroiditis among girls, before investigating papillomavirus vaccination as a potential risk factor. Methods: Observational cohort study including girls aged 9-18 years and registered between 2002-2016 in the Spanish Primary Care Database for Pharmacoepidemiological Research. Girls were followed until a thyroiditis occurred, 19 years of age, left the cohort, died, or the study ended. Anonymized records were reviewed for diagnosis confirmation (endocrine discharge letter and/or free-text comments) in a random sample. Incidence rate (IR) per 105 person years (/105 py) was estimated. Results: The cohort numbered 480,169 girls, of whom 641 had a record of thyroiditis: 346 autoimmune thyroiditis; 17 thyroiditis of other types; and 278 unspecified. Incidence of recorded thyroiditis increased with age, from 23.96 at age 9 years to 47.91 at age 14 years, and stabilized around 31.06-34.43 among girls aged 15-18 years. Of the 98 records reviewed, 60.2% were 'confirmed' cases, 32.7% 'possible' and 7.1% were discarded. After correction for discarded cases, IR=20.83 'confirmed' cases, increasing to 32.12/105 py when 'confirmed' plus 'possible' cases were included. Between 2002-2005, incidences were lower (16.28 and 20.93 cases/105 py) than in the period 2007-2016 (21.17 and 33.78 cases/105 py) for 'confirmed' and 'confirmed' plus 'possible', respectively. Conclusion: Two-thirds of the recorded thyroiditis included confirmatory evidence. The incidence of thyroiditis among girls increased with age and in the later period, and remained stable among girls aged 15-18 years.

Initial Therapy, Regimen Change, and Persistence in a Spanish Cohort of Newly Treated Type 2 Diabetes Patients: A Retrospective, Observational Study Using Real-World Data.

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.

Drug Utilization Pattern of Antibiotics: The Role of Age, Sex and Municipalities in Determining Variation.

PURPOSE: The purpose was to analyze drug prescription and antibiotic use by age and sex in Italy's Campania Region, and to estimate the distribution of prescription rates in children (≤14 years old), adults (between 15 and 65 years old), and older adults (≥65 years old) at a municipality level. METHODS: This was a retrospective analysis of pharmacy records in Campania (Southern Italy), in 2016. Difference in antibiotic prescriptions in different age groups was assessed by prevalence rates. Age-adjusted prevalence rates were categorized into quintiles and mapped by the patient's municipality of residence. Relationship between prevalence rates for the different age groups was estimated using the non-parametric Spearman rank correlation test. RESULTS: There were 2,738,118 were patients with at least one antibiotic prescription. Antibiotics prescription was higher in children aged <5 years and in the older adults aged >70 years. Prevalence rate distribution was different among municipalities in all age groups. A positive correlation between the rank distribution of prevalence rates at municipality level was identified for children and adults (rs=0.56; P<0.01), adults and the older adults (rs=0.79; P<0.01), and children and the older adults (rs=0.46; P<0.01). Among the studied age groups, the most prescribed antibiotic class was penicillin (except the older adults aged ≥85 years) ranging from 45% in children to 27.2% in the older adults. Fluoroquinolones were the least prescribed antibiotic class, ranging from 0.2% in children to 30.2% in the older adults. CONCLUSION: A considerably high use of antibiotic drugs has been detected in Campania Region, with values exceeding the regional and national average. Prescriptions at municipal level differ from one age group to another. Antibiotic use is often unjustified, and to decrease the number of prescriptions and improve their appropriateness, several measures at territorial level are recommended.

Treatment Patterns of Diabetes in Italy: A Population-Based Study.

Background: The steady increase in type 2 diabetes prevalence and the availability of new antidiabetic drugs (AD) have risen the use of these drugs with a change in the patterns of specific drug utilization. The complexity of this treatment is due to successive treatment initiation, switching and addition in order to maintain glycaemic control. The aim of this study was to describe the utilization patterns of ADs at initiation, treatment addition, and switching profiles and to measure factors influencing persistence to therapy. Methods: Retrospective observational study. Data were retrieved from the Campania Regional Database for Medication Consumption. Population consisted of patients receiving at least one prescription of ADs between January 1 and December 31, 2016. We calculated time to treatment switching or add-on as median number of days and interquartile range (IQR). Persistence rates were estimated using the Kaplan-Meier method. We used Cox regression models to estimate the likelihood of non-persistence over 1 year of follow-up. Hazard ratios and 95% confidence intervals were calculated. Results: Of 14,679 patients, 86.9% started with monotherapy and 13.1% with combination therapy. Most common initial treatment was metformin in both monotherapy and combination therapy. First-line prescription of sulfonylurea was observed in 6.9% of patients aged 60-79 years and in 10.8% of patients aged ≥80 years. Patients starting with metformin showed fewer treatment modifications (10.4%) compared to patients initiating with sulfonylureas (35.2%). Newer ADs were utilized during treatment progression. Patients who initiated with sulfonylurea were approximately 70% more likely to discontinue treatment compared to those initiated on metformin. Oldest age group (≥80 years) was more likely to be non-persistent, and likelihood of non-persistence was highest in polymedicated patients. Patients changing therapy were more likely to be persistent. Conclusions: Our results show that treatment of T2D in Italy is consistent with clinical guidelines. Even if newer ADs were utilized during disease progression, they seem not to be preferred in patients with a higher comorbidity score, although these patients could benefit from this kind of treatment. Our study highlights patients' characteristics that might help identify those who would benefit from counselling from their health-care practitioner on better AD usage.

Adherencia al tratamiento de hipertensión arterial, hipercolesterolemia y diabetes en población anciana de una cohorte española / Adherence to treatment of hypertension, hypercholesterolaemia and diabetes in an elderly population of a Spanish cohort

Antecedentes y objetivo: Varios estudios han puesto de manifiesto un cumplimiento terapéutico subóptimo en la población general, sobre todo en ancianos y en enfermos crónicos. El objetivo de este estudio es describir la adherencia al tratamiento de diabetes mellitus, dislipidemia e hipertensión arterial, e identificar los factores que la influencian. Material y métodos: Estudio observacional transversal retrospectivo sobre 16.208 pacientes mayores de 65 años de la Cohorte EpiChron, que iniciaron tratamiento en monoterapia de un antidiabético, un hipolipidemiante o un antihipertensivo en 2010. La adherencia se midió mediante el cálculo de la relación de posesión de medicación durante un año de seguimiento, considerándose adherentes los casos con posesión de medicación ≥80%. Se realizó un estudio descriptivo y un modelo de regresión logística para identificar los factores predictores de baja adherencia. Resultados: La adherencia a los antidiabéticos, antihipertensivos e hipolipidemiantes fue del 72,4; 50,7 y 44,3%, respectivamente. Se observó un aumento en la adherencia del 3-8% por cada enfermedad crónica adicional del paciente. La presencia de enfermedad mental no afectó a la adherencia, y el sexo, edad y número de fármacos prescritos no presentaron efectos consistentes. Conclusiones: Los resultados obtenidos ponen de manifiesto una adherencia al tratamiento subóptima en las enfermedades crónicas estudiadas. La adherencia aumentó con el número de enfermedades crónicas, mientras que sexo, edad y número de fármacos no presentaron un efecto consistente. Es necesario investigar si existen otros factores que puedan influir en la adherencia terapéutica, ya que su mejora puede tener mayor impacto en la salud que cualquier avance en las terapias

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

Patterns of multimorbidity and polypharmacy in young and adult population: Systematic associations among chronic diseases and drugs using factor analysis.

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.

Adherence to treatment of hypertension, hypercholesterolaemia and diabetes in an elderly population of a Spanish cohort. / Adherencia al tratamiento de hipertensión arterial, hipercolesterolemia y diabetes en población anciana de una cohorte española.

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.

Hipovitaminosis D: buscando la evidencia / Hypovitaminosis D: Searching for the evidence

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