Search Results (28)

Background/Objectives: Artificial intelligence (AI) plays an important role in real-world health research. It can address the complexities of chronic diseases and their associated negative outcomes. This systematic review aims to identify the applications of AI that utilize real-world health data for populations with multiple chronic conditions. Methods: A systematic search was performed in MEDLINE and EMBASE following PRISMA guidelines. Studies were included if they applied AI methods using data from electronic health records for patients with multimorbidity. Results: Forty-four studies met the inclusion criteria. The review revealed AI applications identifying disease clusters, predicting comorbidities, and estimating health outcomes such as mortality, adverse drug reactions, and hospital readmissions. Commonly used AI techniques included clustering methods, XGBoost, random forest, and neural networks. These methods helped identify risk factors, predict disease progression, and optimize treatment plans. Conclusions: This study emphasizes the increasing role of AI in understanding and managing multimorbidity. Integrating AI into healthcare systems can enhance resource allocation, improve care delivery efficiency, and support personalized treatment strategies. However, further research is needed to overcome existing limitations, particularly the lack of standardized performance metrics, which affects model comparability. Future research should adhere to commonly recommended evaluation practices to improve reproducibility and meta-analysis. Full article

Background: Managing multimorbidity is a major challenge for healthcare systems. Cardiometabolic multimorbidity (CMM) is highly prevalent and linked to increased disease burden, functional decline, and mortality. While most studies focus on cross-sectional analyses, longitudinal approaches are essential for understanding disease progression and identifying patient groups who may benefit from targeted interventions. Objectives: This systematic review synthesises evidence from longitudinal studies on the incidence and progression of CMM, exploring transitions between multimorbidity clusters and their clinical implications. Methods: A systematic search was conducted in MEDLINE and EMBASE following PRISMA guidelines. Studies were included if they employed longitudinal designs and clustering techniques to assess multimorbidity evolution. The quality of evidence was evaluated using the GRADE system. Results: Ten studies met the inclusion criteria. CMM occurs across all age groups and both sexes, showing the highest mortality and functional decline rates. Patients with CMM frequently develop additional cardiometabolic conditions or transition to related clusters. Many also experience neurodegenerative and mental health disorders. Individuals from respiratory multimorbidity clusters often transition to CMM. Moreover, CMM is more prevalent in lower socioeconomic populations. Conclusions: Understanding multimorbidity trajectories enables targeted preventive strategies. Identifying patients with predictable progression can help design adequate and effective interventions, reduce health disparities, and improve healthcare outcomes. Full article

The optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were selected to maximize phenolic recovery while considering environmental and energy sustainability by optimizing extraction efficiency and minimizing solvent and energy usage. HPLC-ESI-QTOF-MS analysis tentatively identified 25 phenolic compounds, including sulfated phenolic acids, phlorotannins, flavonoids, and halophenols, with some reported for the first time in F. vesiculosus, underscoring the complexity of this alga’s metabolome. The antioxidant activity of the optimized extract was evaluated through FRAP (143.7 µmol TE/g), DPPH (EC₅₀ 105.6 µg/mL), and TEAC (189.1 µmol Trolox/g) assays. The optimized process highlights F. vesiculosus as a valuable source of natural antioxidants, with potential applications in biotechnology, cosmetics, and food industries. Full article

Background: Vitiligo is a pigmentation disorder that impacts approximately 0.5% to 2% of the global population. Growing interest surrounds the comorbidities associated with vitiligo. This study aimed to describe the socio-demographic characteristics of the patients with vitiligo in Aragón (Spain) and to investigate their associated comorbidities. Methods: A retrospective observational study was conducted using clinical data from individuals in the EpiChron Cohort (reference population of 1.3 million) who were diagnosed with vitiligo between 1 January and 31 December 2019. The prevalence of chronic comorbidities was calculated using logistic regression models, obtaining the odds ratio (OR) of each comorbidity (dependent variable) according to the presence or absence of vitiligo (independent variable). We used a cut-off point for a statistical significance of p-value < 0.05. Results: In total, 218 patients diagnosed with vitiligo were analyzed. The mean age was 44.0 years, and 56.42% were female. The largest proportion of patients (34.86%) were aged between 18 and 44 years. Among all vitiligo patients included, 71.5% presented multimorbidity, with an average of 3.21 diagnosed comorbidities. The conditions most frequently associated with vitiligo included thyroid disorders (OR: 3.01, p < 0.001), ocular and hearing abnormalities (OR: 1.54, p < 0.020), inflammatory skin disorders (OR: 2.21, p < 0.001), connective tissue diseases (OR: 1.84, p < 0.007), lower respiratory tract diseases (OR: 1.78, p < 0.014), urinary tract infections (OR: 1.69, p < 0.032), and cardiac arrhythmias (OR 1.84, p < 0.034). Conclusions: This research highlights the importance of understanding the broader health implications of vitiligo and provides a foundation for further exploration into the complex interplay between this dermatologic condition and a diverse range of comorbidities. Full article

Background/Objectives: Chronic liver disease (CLD) is highly relevant in clinical practice due to its increasing incidence and associated mortality. We aimed to exhaustively characterize the multimorbidity of patients with CLD. Methods: This is a retrospective observational study of patients aged 18 years and older with a diagnosis of CLD in 2015 in the EpiChron Cohort (Spain). We analyzed the prevalence of comorbidities according to sex and age, conducted a logistic regression analysis with CLD as the independent variable and each of the comorbidities as dependent variables to obtain odds ratios (OR) adjusted for age and sex, and performed an exploratory factor analysis to identify the presence of multimorbidity patterns. Results: A total of 6836 adults had a diagnosis of CLD (mean age 61.6 years; 62.5% women), with an average of 13 co-existing chronic conditions. Arterial hypertension, lipid metabolism disorders, diabetes, obesity, and musculoskeletal diseases were the most frequent diseases. From the list of 110 chronic conditions analyzed, 75 were systematically associated with CLD, including (OR, 95% confidence interval) chronic pancreatitis (41.2, 33.5–50.6) and inherited metabolic disorders (14.9, 11.8–18.8). Three multimorbidity patterns were identified in both men and women, including cardiovascular, metabolic-geriatric, and mental-substance use, with some differences by sex. Conclusions: Multimorbidity is the norm in patients with CLD. Our results reveal that a comprehensive and integral approach based on person-centered care, which should take into account their entire spectrum of multimorbidity, is necessary during the care of this type of patient in clinical practice. Full article

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. Full article

Introduction: Psoriasis is a chronic disease of the skin with a prevalence of 2% in the general population. The high prevalence of psoriasis has prompted the study of its comorbidities in recent decades. We designed a study to determine the prevalence of psoriasis in a large-scale, population-based cohort, to exhaustively describe its comorbidities, and to analyze which diseases are associated with psoriasis. Methods: Retrospective, observational study based on the clinical information contained in the electronic health records of the individuals in the EpiChron Cohort with a diagnosis of psoriasis (31,178 individuals) in 2019. We used logistic regression models and calculated the likelihood of the occurrence of each comorbidity based on the presence of psoriasis (p-value < 0.05). Results: The prevalence of psoriasis was 2.84%, and it was more prevalent in men (3.31% vs. 2.43%). The most frequent chronic comorbidities were disorders of lipid metabolism (35.87%), hypertension (35.50%), and other nutritional-endocrine-metabolic disorders (21.79%). The conditions most associated with psoriasis were (odds ratio; 95% confidence interval) tuberculosis (2.36; 1.24–4.49), cystic fibrosis (2.15; 1.25–3.69), amongst others. We did not find a significant association between psoriasis and hypertension or neoplasms (0.90; 0.86–0.95). Conclusions: This study revealed significant associations between psoriasis and cardiac, psychological, and musculoskeletal comorbidities. Full article

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. Full article

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. Full article

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. Full article

Background: Atopic dermatitis (AD) is associated with different comorbidities. Methods: Retrospective, observational study based on clinical information from the individuals of the EpiChron Cohort Study (Aragon, Spain) with a diagnosis of AD between 1 January 2010 and 31 December 2018. We calculated the tetrachoric correlations of each pair of comorbidities to analyze the weight of the association between them. We used a cut-off point for statistical significance of p-value < 0.01. Results: The prevalence of AD in the EpiChron Cohort was 3.83%. The most frequently found comorbidities were respiratory, cardio-metabolic, cardiovascular, and mental health disorders. Comorbidities were combined into 17 disease patterns (15 in men and 11 in women), with some sex and age specificities. An infectious respiratory pattern was the most consistently described pattern across all ages and sexes, followed by a cardiometabolic pattern that appeared in patients over 18 years of age. Conclusions: Our study revealed the presence of different clinically meaningful comorbidity patterns in patients with AD. Our results can help to identify which comorbidities deserve special attention in these types of patients and to better understand the physio-pathological mechanisms underlying the disease associations identified. Further studies are encouraged to validate the results obtained in different clinical settings and populations. Full article

Potentially inappropriate medication (PIM) increases adverse drug reactions and mortality, especially in excessively polymedicated patients. General practitioners are often in charge of this process. Some tools have been created to support them in this matter. This study aimed to measure the amount of potentially inappropriate medication among excessively polymedicated patients using several supporting tools and assess the feasibility of these tools in primary care. Several explicit deprescribing criteria were used to identify potentially inappropriate medications. The level of agreement between all the criteria and the acceptance by the general practitioner (GP) was also measured. We analysed whether the drugs proposed for deprescribing were eventually withdrawn after twelve months. The total number of drugs prescribed was 2038. Six hundred and forty-nine drugs (31.8%) were considered potentially inappropriate by at least one of the tools. GPs agreed with the tools in 56.7% of the cases. In a 12-month period, 109 drugs, representing 29.6% of the drugs that GPs agreed to deprescribe, were withdrawn. Elderly excessively polymedicated patients accumulated a great number of PIMs. The use of deprescribing supporting tools, such as explicit criteria, is feasible in primary care, and these tools are well accepted by the GPs. However, eventual withdrawal was carried out in less than half of the cases. Full article

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. Full article

(1) Purpose: To investigate a complex MULTIPAP intervention that implements the Ariadne principles in a primary care population of young-elderly patients with multimorbidity and polypharmacy and to evaluate its effectiveness for improving the appropriateness of prescriptions. (2) Methods: A pragmatic cluster-randomized clinical trial was conducted involving 38 family practices in Spain. Patients aged 65–74 years with multimorbidity and polypharmacy were recruited. Family physicians (FPs) were randomly allocated to continue usual care or to provide the MULTIPAP intervention based on the Ariadne principles with two components: FP training (eMULTIPAP) and FP patient interviews. The primary outcome was the appropriateness of prescribing, measured as the between-group difference in the mean Medication Appropriateness Index (MAI) score change from the baseline to the 6-month follow-up. The secondary outcomes were quality of life (EQ-5D-5 L), patient perceptions of shared decision making (collaboRATE), use of health services, treatment adherence, and incidence of drug adverse events (all at 1 year), using multi-level regression models, with FP as a random effect. (3) Results: We recruited 117 FPs and 593 of their patients. In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was −2.42 (95% CI from −4.27 to −0.59) and, between baseline and a 12-month follow-up was −3.40 (95% CI from −5.45 to −1.34). There were no significant differences in any other secondary outcomes. (4) Conclusions: The MULTIPAP intervention improved medication appropriateness sustainably over the follow-up time. The small magnitude of the effect, however, advises caution in the interpretation of the results given the paucity of evidence for the clinical benefit of the observed change in the MAI. Trial registration: Clinicaltrials.gov NCT02866799. Full article

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. Full article