Polypharmacy Patterns in Multimorbid Older People with Cardiovascular Disease : Longitudinal Study

(1) Introduction: Cardiovascular disease is associated with high mortality, especially in older people. This study aimed to characterize the evolution of combined multimorbidity and polypharmacy patterns in older people with different cardiovascular disease profiles. (2) Material and methods: This longitudinal study drew data from the Information System for Research in Primary Care in people aged 65 to 99 years with profiles of cardiovascular multimorbidity. Combined patterns of multimorbidity and polypharmacy were analysed using fuzzy c-means clustering techniques and hidden Markov models. The prevalence, observed/expected ratio, and exclusivity of chronic diseases and/or groups of these with the corresponding medication were described. (3) Results: The study included 114,516 people, mostly men (59.6%) with a mean age of 78.8 years and a high prevalence of polypharmacy (83.5%). The following patterns were identified: Mental, behavioural, digestive and cerebrovascular ; Neuropathy, autoimmune and musculoskeletal ; Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological ; Non-specific ; Multisystemic ; Respiratory, cardiovascular, behavioural and genitourinary ; Diabetes and ischemic cardiopathy ; and Cardiac. The prevalence of overrepresented health problems and drugs remained stable over the years, although by study end, cohort survivors had more polypharmacy and multimorbidity. Most people followed the same pattern over time; the most frequent transitions were from Non-specific to Mental, behavioural, digestive and cerebrovascular and from Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological to Non-specific. (4) Conclusions: Eight combined multimorbidity and polypharmacy patterns, differentiated by sex, remained stable over follow-up. Understanding the behaviour of different diseases and drugs can help design individualised interventions in populations with clinical complexity

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

Altres ajuts: This manuscript is part of a PhD being undertaken by MGC at the Public Health Department (Departament de Pediatria, d'Obstetrícia i Ginecologia i de Medicina Preventiva) at the Universitat Autònoma de Barcelona. This work was supported by a pre-doctoral grant from Catalan Health Institute in Barcelona; by the Catalan Society of General Practitioners (CAMFiC) and by SIDIAP grant to MGC in 2015; this latter organization allowed us to explore their dataset to obtain the results. The funders had no role in the study design or data collection, analysis, and interpretation, writing of the manuscript, and decision to submit for publication.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

Patrones de multimorbilidad en adultos jóvenes en Cataluña : un análisis de clústeres

Identificar los patrones de multimorbilidad en pacientes de 19-44 años atendidos en atención primaria en Cataluña en el año 2010. Estudio descriptivo transversal. Doscientos cincuenta y un centros de salud. Fueron 530.798 personas con multimorbilidad de 19-44 años. La multimorbilidad fue definida como la coexistencia de ≥2 diagnósticos de la Clasificación Internacional de Enfermedades registrados en la historia clínica informatizada. Los patrones de multimorbilidad fueron identificados a través de un análisis jerárquico de clústeres y descritos por sexo y grupos de edad (19-24 y 25-44 años). De las 882.708 personas de la población inicial, 530.798 (60,1%) presentaron multimorbilidad. La media de edad fue de 33,0 años (DT: 7,0) y el 53,3% fueron mujeres. La multimorbilidad fue más alta en el grupo de 25-44 años respecto al grupo más joven (60,5 vs. 58,1%, p < 0,001), siendo más alta en las mujeres. El clúster más prevalente en todos los estratos estuvo constituido por caries dental, tabaquismo, dorsalgia, resfriado común y otros trastornos de ansiedad. En ambos sexos, en los estratos de 25-44 años apareció el patrón cardiovascular-endocrino-metabólico (obesidad, dislipidemias e hipertensión arterial). La multimorbilidad afecta a más de la mitad de personas entre los 19-44 años de edad. El clúster más prevalente está formado por diagnósticos que agrupan enfermedades comunes (caries dental, resfriado común, tabaquismo, trastornos de ansiedad y dorsalgias). Otro patrón a destacar es el cardiovascular-endocrino-metabólico en el grupo de 25-44. El conocimiento de los patrones de multimorbilidad en adultos jóvenes permitiría un enfoque preventivo

Soft clustering using real-world data for the identification of multimorbidity patterns in an elderly population: Cross-sectional study in a Mediterranean population

The aim of this study was to identify, with soft clustering methods, multimorbidity patterns in the electronic health records of a population =65 years, and to analyse such patterns in accordance with the different prevalence cut-off points applied. Fuzzy cluster analysis allows individuals to be linked simultaneously to multiple clusters and is more consistent with clinical experience than other approaches frequently found in the literature.Peer ReviewedPostprint (published version

Impact of Glucose-Lowering Agents on the Risk of Cancer in Type 2 Diabetic Patients. The Barcelona Case-Control Study

The aim of the present study is to evaluate the impact of glucose-lowering agents in the risk of cancer in a large type 2 diabetic population. A nested case-control study was conducted within a defined cohort (275,164 type 2 diabetic patients attending 16 Primary Health Care Centers of Barcelona). Cases (n = 1,040) comprised those subjects with any cancer diagnosed between 2008 and 2010, registered at the Cancer Registry of Hospital Vall d'Hebron (Barcelona). Three control subjects for each case (n = 3,120) were matched by age, sex, diabetes duration, and geographical area. The treatments analyzed (within 3 years prior to cancer diagnosis) were: insulin glargine, insulin detemir, human insulin, fast-acting insulin and analogues, metformin, sulfonylureas, repaglinide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and alpha glucosidase inhibitors. Conditional logistic regressions were used to calculate the risk of cancer associated with the use of each drug adjusted by age, BMI, dose and duration of treatment, alcohol use, smoking habit, and diabetes duration. No differences were observed between case and control subjects for the proportion, dose or duration of exposure to each treatment. None of the types of insulin and oral agents analyzed showed a significant increase in the risk of cancer. Moreover, no cancer risk was observed when glargine was used alone or in combination with metformin. Our results suggest that diabetes treatment does not influence the risk of cancer associated with type 2 diabetes. Therefore, an eventual increase of cancer should not be a reason for biasing the selection of any glucose-lowering treatment in type 2 diabetic population

12-year evolution of multimorbidity patterns among older adults based on Hidden Markov Models

Background: The evolution of multimorbidity patterns during aging is still an under-researched area. We lack evidence concerning the time spent by older adults within one same multimorbidity pattern, and their transitional probability across different patterns when further chronic diseases arise. The aim of this study is to fill this gap by exploring multimorbidity patterns across decades of age in older adults, and longitudinal dynamics among these patterns. Methods: Longitudinal study based on the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) on adults ≥60 years (N=3,363). Hidden Markov Models were applied to model the temporal evolution of both multimorbidity patterns and individuals' transitions over a 12-year follow-up. Findings: Within the study population (mean age 76.1 years, 66.6% female), 87.2% had ≥2 chronic conditions at baseline. Four longitudinal multimorbidity patterns were identified for each decade. Individuals in all decades showed the shortest permanence time in an Unspecific pattern lacking any overrepresented diseases (range: 4.6-10.9 years), but the pattern with the longest permanence time varied by age. Sexagenarians remained longest in the Psychiatric-endocrine and sensorial pattern (15.4 years); septuagenarians in the Neuro-vascular and skin-sensorial pattern (11.0 years); and octogenarians and beyond in the Neuro-sensorial pattern (8.9 years). Transition probabilities varied across decades, sexagenarians showing the highest levels of stability. Interpretation: Our findings highlight the dynamism and heterogeneity underlying multimorbidity by quantifying the varying permanence times and transition probabilities across patterns in different decades. With increasing age, older adults experience decreasing stability and progressively shorter permanence time within one same multimorbidity pattern

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

This manuscript constitutes a part of the PhD thesis of MGC in the Public Health Department of the Universitat Autònoma de Barcelona. This work was supported by a pre-doctoral grant from Catalan Health Institute in Barcelona; by the Catalan Society of General Practitioners (CAMFiC) and by SIDIAP grant to MGC in 2015; this latter organization allowed us to explore their dataset to obtain the results. The funders had no role in the study design or data collection, analysis, and interpretation, writing of the manuscript, and decision to submit for publication.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. 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. 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. 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. The online version of this article (10.1186/s12877-018-0705-7) contains supplementary material, which is available to authorized users

Effect of the comprehensive smoke-free law on time trends in smoking behaviour in primary healthcare patients in Spain : A longitudinal observational study

Altres ajuts: Funding This project has been funded by the Carlos III Health Institute through the Network for Prevention and Health Promotion in Primary Care (redIAPP, RD12/0005/0001; RD16/0007/0001), and by European Union ERDF funds.Objective This study aimed to analyse the impact of comprehensive smoke-free legislation (SFL) on the prevalence and incidence of adult smoking in primary healthcare (PHC) patients from three Spanish regions, overall and stratified by sex. Design Longitudinal observational study conducted between 2008 and 2013. Setting 66 PHC teams in Catalonia, Navarre and the Balearic Islands (Spain). Participants Population over 15 years of age assigned to PHC teams. Primary and secondary outcomes measures Quarterly age-standardised prevalence of non-smoker, smoker and ex-smoker and incidence of new smoker, new ex-smoker and ex-smoker relapse rates were estimated with data retrieved from PHC electronic health records. Joinpoint analysis was used to analyse the trends of age-standardised prevalence and incidence rates. Trends were expressed as annual percentage change and average annual percent change. Results The overall standardised smoker prevalence rate showed a significant downward trend (higher in men than women) and the overall standardised ex-smoker prevalence rate showed a significant increased trend (higher in women than men) in the three regions. Standardised smoker and ex-smoker prevalence rates were higher for men than women in all regions. With regard to overall trends of incidence rates, new smokers decreased significantly in Catalonia and Navarre and similarly in men and women, new ex-smokers decreased significantly and more in men in Catalonia and the Balearic Islands, and ex-smoker relapse increased in Catalonia (particularly in women) and decreased in Navarre. Conclusions Trends in smoking behaviour in PHC patients remain unchanged after the implementation of comprehensive SFL. The impact of the comprehensive SFL might have been lessened by the effect of the preceding partial SFL

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

Altres ajuts: European Regional Development Fund (IP12/00427)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. 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. 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. 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

Mycobacterium manresensis induces trained immunity in vitro

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days. Biological sciences; Molecular biology; Immunology; Microbiolog