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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 3 chronic 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.

Resumen Antecedentes y objetivo Varios estudios han puesto de manifiesto un cumplimiento terapeutico suboptimo en la poblacion general, sobre todo en ancianos y en enfermos cronicos. El objetivo de este estudio es describir la adherencia al tratamiento de diabetes mellitus, dislipidemia e hipertension arterial, e identificar los factores que la influencian. Material y metodos Estudio observacional transversal retrospectivo sobre 16.208 pacientes mayores de 65 anos de la Cohorte EpiChron, que iniciaron tratamiento en monoterapia de un antidiabetico, un hipolipidemiante o un antihipertensivo en 2010. La adherencia se midio mediante el calculo de la relacion de posesion de medicacion durante un ano de seguimiento, considerandose adherentes los casos con posesion de medicacion ≥80%. Se realizo un estudio descriptivo y un modelo de regresion logistica para identificar los factores predictores de baja adherencia. Resultados La adherencia a los antidiabeticos, antihipertensivos e hipolipidemiantes fue del 72,4; 50,7 y 44,3%, respectivamente. Se observo un aumento en la adherencia del 3-8% por cada enfermedad cronica adicional del paciente. La presencia de enfermedad mental no afecto a la adherencia, y el sexo, edad y numero de farmacos prescritos no presentaron efectos consistentes. Conclusiones Los resultados obtenidos ponen de manifiesto una adherencia al tratamiento suboptima en las enfermedades cronicas estudiadas. La adherencia aumento con el numero de enfermedades cronicas, mientras que sexo, edad y numero de farmacos no presentaron un efecto consistente. Es necesario investigar si existen otros factores que puedan influir en la adherencia terapeutica, ya que su mejora puede tener mayor impacto en la salud que cualquier avance en las terapias.

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.

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.

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 (Arag&oacute, n, Spain). The population was stratified by sex and into three age sub-populations (80&ndash, 89, 90&ndash, 99, and &ge, 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.

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. Publisher PDF

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&ndash, 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&ndash, 0.63), living in rural (HR 0.79) or more deprived areas (HR 0.77&ndash, 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.

Enrica Menditto,1,* Caitriona Cahir,2,* Mercedes Aza-Pascual-Salcedo,3,4 Dario Bruzzese,5 Beatriz Poblador-Plou,3 Sara Malo,6 Elisio Costa,7 Francisca González-Rubio,3,4,6 Antonio Gimeno-Miguel,3 Valentina Orlando,1 Przemyslaw Kardas,8 Alexandra Prados-Torres3 1CIRFF, Center of Pharmacoeconomics, University of Naples Federico II, Naples, Italy; 2Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; 3Aragon Health Sciences Institute (IACS), IIS Aragón, REDISSEC ISCIII, Madrid, Spain; 4Aragon Health Service (SALUD), Aragon, Spain; 5Department of Public Health, Federico II University, Naples, Italy; 6University of Zaragoza, Zaragoza, Spain; 7UCIBIO, REQUINTE, Faculty of Pharmacy, Porto4ageing Reference Site, University of Porto, Porto, Portugal; 8Department of Family Medicine, Medical University of Lodz, Lodz, Poland*These authors contributed equally to this workPurpose: The purpose of this study was to evaluate and compare medication adherence to chronic therapies in older populations across different regions in Europe.Methods: This explorative study applied a harmonized method of data extraction and analysis from pharmacy claims databases of three European countries to compare medication adherence at a cross-country level. Data were obtained for the period between January 1, 2010, and December 31, 2011. Patients (aged ≥65 years) who newly initiated to oral antidiabetics, antihyperlipidemics, or antiosteoporotics were identified and followed for over a 12-month period. Main outcome measures were medication adherence (medication possession ratio, [MPR]; implementation) and persistence on index treatment. All country-specific data sets were prepared by employing a common data input model. Outcome measures were calculated for each country and pooled using random effect models.Results: In total, 39,186 new users were analyzed. In pooled data from the three countries, suboptimal implementation (MPR 50% of older people non-adherent to antihyperlipidemics and antiosteoporotics in the three European cohorts. However, the degree of variability in adherence rates among the three countries was high. A harmonized method of data extraction and analysis across health-related database in Europe is useful to compare medication-taking behavior at a cross-country level. Keywords: drug utilization, medication adherence, medication persistence, prescribing

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

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 purpose 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 was composed by 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 one year of follow-up. Hazard ratios and 95% confidence intervals were calculated. Results: Of 14,679 subjects, 86.9% started with monotherapy and 13.1% with combination therapy. Most common initial treatment was metformin, both in 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. Subjects initiated with sulfonylurea were approximately 70% more likely to discontinue treatment compared to those initiated on metformin. Oldest age group (≥80years) 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 may help identify those who would benefit from counselling from their health-care practitioner on better ADs usage.

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.

The purpose of this prospective study is to determine the relative incidence of Alzheimer’s disease in patients treated for at least three years, with sulodexide (n = 46, 76.48 ± 7.02 years old) or acenocoumarol (n = 47, 78.21 ± 6.66 years old) in order to prevent primary and secondary venous thromboembolism and atherothrombotic disease. In the sulodexide group, there was an apparent prevention of cognitive and behavioural impairment (relative incidence: 2.02) compared with acenocoumarol group (relative incidence: 4.86). The favourable results in sulodexide group may be related to their pharmacodynamic actions of inhibition of PAI-1, which may interfere with the pathogenesis of Alzheimer’s disease, and to the role of glutathione and PAI-1 in the β-amyloid system in the brain.

Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen activator (t-PA), accompanied by the oxidative stress and the marked decrease of the main antioxidant—glutathione are fundamental in the bases of elderly pathologies which can cause death. There is some scientific evidence of the relationship between aging, neuro-degenerative diseases, an excessive production of reactive oxygen species and the decrease of proteolysis in brain. The cerebral plasminogen/plasmin system represents the essential proteolytic mechanism that degrades amyloid peptides (β-amyloidosis) for action of plasmin with effectiveness. This physiologic process is being considered as a preventive neurodegenerative mechanism. At the same time, the decrease of glutathione levels in aging entails a decrease of cerebral plasmin activity and a progressive descent of t-PA activity due to a descent in t-PA expression and an increase in PAI production. All of them entail an increment of amyloid beta peptides (Aβ) production and a lower level of their clearance. Both mechanisms, oxidative stress, direct consequence of the oxygenate metabolism of aerobics cells, and changes in the systemic fibrinolysis and cerebral b-amyloidolytic activity, play a very important role in thromboembolic disease, metabolic syndrome—obesity, insulin resistance, hyperglycemia—, type 2 Diabetes Mellitus and Alzheimer’s disease, clinical processes that accompany the aging. In this revision we show the importance of the interaction between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis of the importance of a therapeutic strategy using the inhibition of PAI-1 as a goal, because it is increased in the different aging pathologic processes.

Why was the cohort set up? Greater life expectancy in Europe over the past few decades has been translated into an increasing burden of chronic diseases that accumulate as the population ages, whereas acute infectious diseases have been progressively pushed into the background. The incidence of conditions such as hypertension, obesity and asthma has increased dramatically worldwide, and cancer, diabetes and respiratory and cardiovascular diseases are responsible for almost 70% of global deaths. Concurrently, the prevalence of multimorbidity (as of people affected by more than one chronic disorder) is also increasing and appears as the most common chronic condition at present. Multimorbidity affects almost 3 in 4 individuals aged 65 years and older, although it represents a problem not only for the elderly but also for adult and even young populations, at whom prevention strategies should aim. People affected by multimorbidity often experience fragmentation of care, greater and inadequate use of health services and polypharmacy, which in turn may increase the risk of low adherence and adverse drug reactions. All of this leads to individuals’ quality of life deterioration and higher risk of mortality. Besides, handling patients with multimorbidity represents a daily challenge for physicians and health systems...