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

IntroductionThe 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.MethodsWe 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.ResultsWe 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.DiscussionWell-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

Prescribed drugs and self-directed violence: a descriptive study in the spanish pharmacovigilance database

Self-inflicted violence is a major and growing public health problem and its prediction and prevention is challenging for healthcare systems worldwide. Our aim was to identify prescribed drugs associated with self-directed violent behaviors in Spain. A descriptive, longitudinal and retrospective study of spontaneous reports of adverse drug reactions corresponding to self-directed violence was recorded in the Spanish Pharmacovigilance Database (FEDRA®) from 1984 to 31 March 2021. A total of 710 cases were reported in the study period. The mean age was 45.52 years (range 1–94). There were no gender differences except in children, where most reports were of male children. The main therapeutic groups that were involved included drugs for the nervous system (64.5%) and anti-infectives for systemic use (13.2%). The most commonly reported drugs were varenicline, fluoxetine, lorazepam, escitalopram, venlafaxine, veralipride, pregabalin, roflumilast and bupropion. There were reports of montelukast, hydroxychloroquine, isotretinoin, methylphenidate, infliximab, natalizumab, ribavirin and efavirenz, which were less known to be involved in self-directed violence. This study shows that self-directed violence is a rare adverse drug reaction, and can be related to the use of some medicines. It is important for healthcare professionals to consider this risk in their clinical praxis, implementing person-centred approaches. Further studies are needed, considering comorbidities and potential interactions

Reports of Symptoms Associated with Supraventricular Arrhythmias as a Serious Adverse Drug Reaction in the Spanish Pharmacovigilance Database

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs

Drug repurposing in oncology: a systematic review of randomized controlled clinical trials

Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer’s disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis

Association between mental health comorbidity and health outcomes in type 2 diabetes mellitus patients.

Type 2 diabetes mellitus (T2D) is often accompanied by chronic diseases, including mental health problems. We aimed at studying mental health comorbidity prevalence in T2D patients and its association with T2D outcomes through a retrospective, observational study of individuals of the EpiChron Cohort (Aragón, Spain) with prevalent T2D in 2011 (n = 63,365). Participants were categorized as having or not mental health comorbidity (i.e., depression, anxiety, schizophrenia, and/or substance use disorder). We performed logistic regression models, controlled for age, sex and comorbidities, to analyse the likelihood of 4-year mortality, 1-year all-cause hospitalization, T2D-hospitalization, and emergency room visit. Mental health comorbidity was observed in 19% of patients. Depression was the most frequent condition, especially in women (20.7% vs. 7.57%). Mortality risk was higher in patients with mental health comorbidity (odds ratio 1.24; 95% confidence interval 1.16-1.31), especially in those with substance use disorder (2.18; 1.84-2.57) and schizophrenia (1.82; 1.50-2.21). Mental health comorbidity also increased the likelihood of all-cause hospitalization (1.16; 1.10-1.23), T2D-hospitalization (1.51; 1.18-1.93) and emergency room visit (1.26; 1.21-1.32). These results suggest that T2D healthcare management should include specific strategies for the early detection and treatment of mental health problems to reduce its impact on health outcomes.This work was supported by Gobierno de Aragón [B01_20R] and the European Regional Development Fund “Construyendo Europa desde Aragón”. The authors sincerely thank Eva Giménez Labrador for her statistical support.S

Multimorbidity Profiles and Infection Severity in COVID-19 Population Using Network Analysis in the Andalusian Health Population Database

Identifying the population at risk of COVID-19 infection severity is a priority for clinicians and health systems. Most studies to date have only focused on the effect of specific disorders on infection severity, without considering that patients usually present multiple chronic diseases and that these conditions tend to group together in the form of multimorbidity patterns. In this large-scale epidemiological study, including primary and hospital care information of 166,242 patients with confirmed COVID-19 infection from the Spanish region of Andalusia, we applied network analysis to identify multimorbidity profiles and analyze their impact on the risk of hospitalization and mortality. Our results showed that multimorbidity was a risk factor for COVID-19 severity and that this risk increased with the morbidity burden. Individuals with advanced cardio-metabolic profiles frequently presented the highest infection severity risk in both sexes. The pattern with the highest severity associated in men was present in almost 28.7% of those aged ≥ 80 years and included associations between cardiovascular, respiratory, and metabolic diseases; age-adjusted odds ratio (OR) 95% confidence interval (1.71 (1.44–2.02)). In women, similar patterns were also associated the most with infection severity, in 7% of 65–79-year-olds (1.44 (1.34–1.54)) and in 29% of ≥80-year-olds (1.35 (1.18–1.53)). Patients with mental health patterns also showed one of the highest risks of COVID-19 severity, especially in women. These findings strongly recommend the implementation of personalized approaches to patients with multimorbidity and SARS-CoV-2 infection, especially in the population with high morbidity burden

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