Search Results (1,350)

Background: Vitamin deficiencies remain prevalent worldwide and contribute to chronic disease burden. This study evaluated serum concentrations of vitamins D, A, and E in Italian general practice populations and examined their associations with prevalent chronic diseases. Methods: This multicenter cross-sectional study enrolled 500 adult patients (median age: 60.7 years; 40.4% male) attending 21 general practice offices across Italy between January 2021 and December 2024. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], vitamin A, and vitamin E were measured alongside demographic, clinical, and biochemical parameters. Statistical analyses included chi-square tests, correlation analyses, and stepwise logistic regression. Results: The median 25(OH)D concentration was 20.4 ng/mL, below optimal levels. Vitamin D deficiency was significantly associated with osteoporosis (p = 0.015), arterial hypertension (p = 0.047), and coronary artery disease (p = 0.002). The median vitamin A (654 μg/L) and vitamin E (11.3 mg/L) concentrations were within normal ranges. Notably, elevated vitamin A levels were significantly associated with arterial hypertension (p = 0.005), diabetes mellitus (p = 0.036), and cancer (p = 0.010). In the multivariate analysis, elevated vitamin A levels emerged as an independent predictor of multiple comorbidities (p < 0.001) and cancer presence (p = 0.014), alongside age, male gender, and body mass index. Conclusions: Vitamin D insufficiency is highly prevalent in Italian primary care populations. Vitamin A concentrations show independent associations with multimorbidity and cancer, suggesting a potential negative influence of an animal-based diet, warranting prospective investigation. These findings highlight the importance of comprehensive vitamin assessment in general practice settings. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce morbidity and mortality associated with type II diabetes mellitus, and/or obesity, and/or cardiovascular disease in multiple clinical trials. Their efficacy in reversing cardiovascular disease and mitigating the risk of major adverse cardiac and vascular events has been well studied, with outcome trials consistently demonstrating benefits such as reduced systemic inflammation, improved endothelial function, and favorable metabolic effects. These pleiotropic actions have nearly innumerable potential applications, with a progressively growing interest in using GLP-1 RAs to mitigate increased cardiovascular disease risk secondary to other off-target pharmacologic agents. Given these effects, the potential to utilize GLP-1 RAs for prophylactic cardioprotection before, during, and/or after chemotherapy regimens is of great interest. These effects are thought to be mediated in part through anti-inflammatory and antioxidant mechanisms that counter inflammation and reactive oxygen species-driven myocardial injury central to anthracycline-induced cardiotoxicity (AIC). Anthracyclines, a widely used class of chemotherapeutics for various malignancies, are frequently associated with dose-dependent and often irreversible cardiotoxicity, leading to heart failure, reduced quality of life, and adverse long-term outcomes. For the past three decades, dexrazoxane has been the sole Food and Drug Administration-approved agent for cardioprotection in this setting. However, in the current era of novel therapies with multi-system benefits—such as GLP-1 RAs—we propose a theoretical framework exploring their potential role in mitigating AIC and underscore the need for further clinical investigation in this new arena in the field of cardio-oncology. Full article

Background/Objectives: People experiencing homelessness (PEH) face greater morbidity, multimorbidity, and premature mortality than the general population. Medical data on this population in Gdańsk remain scarce. The aim of this study was to assess the prevalence, age distribution, comorbidity burden, and healthcare utilization of selected neurological and vascular diseases among homeless men in Gdańsk, Poland. Methods: A retrospective secondary analysis was performed using data from 551 men residing in shelters operated by the largest PEH support organization in Gdańsk. A random sample of 226 individuals (95% confidence level) was analyzed, selected by randomization in Microsoft Excel. Data were extracted from interviews, verified medical documentation, and staff records. Results: Mean age was 57.0 (SD 12.9) years (median 60). Among the studied sample, essential (primary) hypertension (20.4%), heart failure (10.2%), atrial fibrillation (8.9%), and chronic obstructive pulmonary disease (8.4%) were the most common conditions. Sequelae of cerebrovascular disease (ICD-10: I69) affected 8.9% of participants; this subgroup was older and had higher rates of disability certification and hospitalization than the overall sample. Epilepsy (12.0%) and polyneuropathy (4.0%) differed in age distribution, disability rates, and comorbidity burden, with the epilepsy subgroup displaying high substance-use prevalence. Overall, 44.0% of the sample had been hospitalized since 2019. Conclusions: Homeless men in Gdańsk present a high burden of neurological and vascular disease at comparatively young ages, along with substantial multimorbidity. These findings highlight structural inequalities in healthcare access and the need for integrated, equity-oriented health and social care interventions. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide and a systemic condition in which outcomes are influenced by respiratory impairment, multimorbidity, exacerbation burden, and functional status. This study aimed to identify multidimensional determinants of all-cause mortality in a population-based cohort of primary care patients with spirometry-confirmed COPD. Methods: We conducted a retrospective population-based cohort study using electronic health records from primary care in the Lleida health region (Catalonia, Spain). Adult patients with spirometry-confirmed COPD (FEV1/FVC < 0.70) between 2019 and 2023 were included. Baseline demographic, clinical, spirometric, functional, and social variables were extracted. Exacerbations in the year prior to baseline were classified as 0, 1, or ≥2 events (and, where available, as moderate vs. severe) using a prespecified operational definition. The primary outcome was all-cause mortality during follow-up (censoring date: 31 December 2023). Time-to-event analyses were performed using Cox proportional hazards models. Results: A total of 2056 patients were included (median age 71 years; 78.4% male). During follow-up, 558 patients died (27.1%). Independent predictors of mortality included male sex, increasing age, current smoking, and prior exacerbations, whereas sufficient physical activity and better lung function (FEV1 % predicted) were protective. Conclusions: Mortality in spirometry-confirmed COPD managed in primary care is driven by a multidimensional vulnerability profile beyond lung function alone. Integrating respiratory, clinical, and functional determinants may improve risk stratification and management in chronic lung disease. Full article

Background: Non-cardiac comorbidities (NCCs) are highly prevalent among patients hospitalized for acute heart failure (HF). However, data from sub-Saharan Africa (SSA) on their distribution across HF phenotypes and association with in-hospital outcomes remain limited. Methods: We prospectively enrolled adults hospitalized with acute HF at a tertiary centre in South Africa between February and November 2023. Ten NCCs were assessed and patients were categorized according to comorbidity burden. The primary outcomes were all-cause in-hospital mortality and length of stay. Multivariable regression and sensitivity analyses were performed to identify predictors of outcomes. Results: Of the 406 patients (mean age 54.9 ± 15.8 years; 51% women), HF with reduced ejection fraction (HFrEF) accounted for 63%, HF with mildly reduced ejection fraction (HFmrEF) for 15%, and HF with preserved ejection fraction (HFpEF) for 21%. The most common NCCs were diabetes (47%), chronic kidney disease (CKD) (46%), obesity (45%), and anaemia (33%). Two-thirds had ≥2 NCCs. The median hospital stay was 8 days (IQR: 5–12) and in-hospital mortality was 3.4% (p > 0.05 across NCC groups). Higher heart rate predicted longer hospitalization, while renin angiotensin system inhibitor (RASi) therapy was associated with shorter stay. Lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score (adjusted odds ratio [aOR] 1.009; 95% confidence interval [CI]: 1.003–1.015) and higher log-transformed NT-proBNP were independently associated with increased in-hospital mortality (aOR 1.85; 95% CI: 1.07–3.50; p = 0.026). Total comorbidity burden was not independently associated with length of stay or in-hospital mortality. Conclusions: Non-cardiac comorbidities are common in acute HF in SSA, and functional status and clinical markers were the strongest predictors of length of stay and in-hospital mortality. Full article

Background: Non-invasive brain stimulation (NIBS) is increasingly used as an adjunctive option in late-life depression (≥60 years), a condition frequently complicated by multimorbidity and incomplete response to standard treatments. Comparative real-world evidence between repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), particularly including functional outcomes, remains limited. Methods: We conducted a retrospective, naturalistic comparative study of 104 depressed inpatients (≥60 years), either unipolar or bipolar, treated with rTMS (n = 48) or tDCS (n = 56) as part of routine care. Depression severity was assessed with the 21-item Hamilton Depression Rating Scale (HDRS21) at baseline, 2 weeks, and 1 month; response was defined as ≥50% HDRS21 score reduction and remission as HDRS21 < 7 at 1 month. Global Assessment of Functioning (GAF) was assessed at admission and discharge (baseline and 1 month). Longitudinal changes were examined using covariate-adjusted mixed-effects models; categorical outcomes were compared using χ² tests. Propensity score matching was applied as an additional approach to reduce confounding due to the observational design. Results: At 1 month, response and remission rates were significantly higher in the rTMS group than in the tDCS group (87.5% vs. 55.4%, p < 0.001; 62.5% vs. 41.1%, p = 0.047, respectively). rTMS showed greater HDRS21 score reductions at 2 weeks and 1 month (Time × Treatment, p < 0.001). GAF scores significantly improved over time in both groups (Time effect, p < 0.001) without between-technique differences (Time × Treatment, p = 0.56), and GAF scores did not differ by response/remission status. Conclusions: In this cohort of inpatients aged ≥ 60 years with depressive episodes, rTMS was associated with greater short-term reductions in HDRS21 scores compared with tDCS, whereas both modalities showed comparable improvements in GAF from admission to discharge. Full article

Background: Chronic non-cancer pain (CNCP) is an increasing global health concern and a multidimensional condition shaped by biological, psychological, social, and cultural factors, with impacts on functioning, quality of life, and healthcare. However, evidence remains fragmented, limiting integrated understanding and care. Objective: This study aimed to synthesize and critically analyze existing evidence on the biological, psychological, social, and cultural dimensions characterizing individuals with CNCP, and their impact on functionality, quality of life, and healthcare. Methodology: An integrative review was conducted following the Whittemore and Knafl framework. Searches were performed in Medline, Cumulative Index of Nursing and Allied Literature Complete (CINAHL), PsycINFO, Scopus, Web of Science, and grey literature in English and Spanish, without time restrictions. Studies were screened using predefined eligibility criteria and appraised with Joanna Briggs Institute tools. Data were systematically extracted and synthesized using thematic analysis to identify key attributes of people living with CNCP. Quantitative findings were summarized descriptively and mapped to thematic domains, while qualitative data were analyzed interpretively. Both evidence streams were integrated through convergent thematic synthesis. Results: Forty-four studies were included, predominantly cross-sectional and observational. Five themes emerged: biological aspects; functioning and quality of life; psychological and mental factors; social support and peer relationships; and social and gender determinants. CNCP was consistently associated with multimorbidity, sleep disturbance, psychological distress, and maladaptive coping, contributing to reduced functional capacity, greater disability, poorer quality of life, and increased healthcare utilization. Socioeconomic disadvantages and environmental constraints were linked to higher pain burden, whereas resilience and social support emerged as protective factors mitigating functional and psychosocial impact. Conclusions: Evidence largely concentrates on biomedical, functional, and psychological dimensions, whereas social determinants and healthcare quality remain comparatively underexplored. Broadening these perspectives is essential to inform public health strategies and support multidisciplinary, equitable care for individuals living with CNCP. Full article

(1) Background: Proactive health behaviors are key to reducing their burden and supporting healthy aging. (2) Methods: We analyzed five waves (2011–2020) of CHARLS data from 1343 middle-aged and older adults (≥45 years) with multimorbidity. An entropy weight method was used to create a composite score for proactive health behaviors, and group-based trajectory modeling identified behavioral trajectories. Multivariate logistic regression and Shapley value decomposition assessed determinants and their relative contributions. Generalized structural equation modeling and latent class analysis were applied to estimate direct and indirect effects across the full sample and key multimorbidity subgroups. (3) Results: Two trajectories emerged: a “declining group” (91.44%) and an “improving group” (8.56%). The improving group was more likely to include younger, urban individuals with higher education, retired status, smaller family size, and lower depression levels. Education (40.67%) and depressive symptoms (31.22%) were the strongest determinants of trajectory. Path analysis showed that higher education and retirement indirectly supported sustained proactive health behaviors by reducing depression. The direct and indirect effects varied across subgroups. (4) Conclusion: The proactive health behaviors of middle-aged and elderly patients with multimorbidity exhibit a declining trend. Future health policies and interventions should prioritize mental health. Full article

Multimorbidity is a key global trend across healthcare fields, including gynecology. It is strongly associated with an overall poorer health status. Statistics indicate that in the 21st century most women experience at least one gynecological disease. Meanwhile, there is a consistent increase in the prevalence of obesity associated with chronic inflammation and hyperestrogenism. Alongside other factors, it leads to a growing prevalence of hyperproliferative diseases of the female reproductive system (FRS), encompassing both benign and malignant conditions. While advanced-stage malignant tumors can be linked to missed detection and wrong checkup strategies, benign neoplasms can compromise the ovarian reserve and thus cause major concerns. The prevailing benign FRS tumors are uterine fibroids (UFs) and benign ovarian tumors (BOTs), including serous and mucinous cystadenomas. It appears that an increase in certain benign FRS tumors is occurring in parallel with a rise in infertility (especially “unexplained infertility”) and reproduction failures, potentially associated with endometrial dysfunction. Thus, the endometrium is currently considered a critical area of research due to its vital role as the site of blastocyst adhesion and implantation, especially in patients with comorbidities. In this context, this article highlights the significance and pathophysiological characteristics of UFs and BOTs and their impact on defective endometrial receptivity. Full article

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide and is driven by complex, interconnected pathophysiological processes, including maladaptive cardiac remodeling, fibrosis, hypertrophy, metabolic dysregulation, and cardiomyocyte loss. MicroRNAs (miRNAs), small non-coding RNAs that act as key post-transcriptional regulators of gene expression, have emerged as important coordinators of these processes across cardiomyocytes and non-myocyte cardiac cell populations. In addition to altered expression patterns, accumulating evidence indicates that miRNA activity is dynamically influenced by regulated biogenesis, maturation, and context-dependent mechanisms of action. Through reversible translational repression and longer-term mRNA destabilization, miRNAs support adaptive responses to acute cardiac stress, whereas their persistent dysregulation contributes to remodeling pathways that promote HF progression. This comprehensive narrative review provides an integrative overview of current knowledge on the role of miRNA networks in shaping the molecular heterogeneity of heart failure across disease stages, phenotypes, and cardiac cell types. Drawing on a broad body of experimental and clinical literature, we discuss advances in understanding miRNA biogenesis, post-transcriptional control, and cell-specific effects, while highlighting conceptual developments rather than applying systematic selection criteria. We further examine the translational and clinical implications of miRNA biology, critically considering the progress of miRNA-based therapeutics alongside the biological and practical challenges that continue to limit their widespread clinical implementation. In parallel, we explore the emerging potential of circulating miRNAs as minimally invasive biomarkers that reflect upstream regulatory stress at the level of RNA processing and post-transcriptional regulation. Finally, we address the growing application of artificial intelligence and machine learning approaches to high-dimensional miRNA datasets, which enable integrative analyses across clinical, imaging, and multi-omics domains and support biomarker discovery, patient stratification, and prediction of therapeutic response. Collectively, miRNA biology, supported by systems-level and AI-driven analytical frameworks, offers a unifying perspective for understanding, classifying, and monitoring cardiac remodeling in heart failure. Full article

Background/Objectives: An increasing proportion of patients with Type 2 diabetes mellitus (T2DM) are classified as high risk, often presenting with multimorbidity, functional vulnerability, and complex treatments. This study compared the sociodemographic, functional, clinical, therapeutic, and healthcare utilization profiles of high-risk chronic patients with and without T2DM in primary health care. Methods: A cross-sectional study included adults classified as high-risk chronic patients in primary health care electronic health records in the Madrid Region (30 April 2021). Sociodemographic, functional, clinical, lifestyle, pharmacological variables, and primary health care services utilization were analyzed. Multivariate logistic regression identified factors independently associated with T2DM. Results: Among 163,188 high-risk chronic patients, 41.5% had T2DM. Patients with T2DM were older, more often male, and had a comparable deprivation index values to non-diabetic patients. They showed higher functional dependency and greater need for informal caregiving. Clinically, patients with T2DM had a higher burden of chronic conditions and a predominance of cardiometabolic, hematological and renal comorbidities, whereas non-diabetic patients exhibited more neuropsychiatric, chronic infectious, oncological and respiratory profiles. Polypharmacy was more frequent in T2DM patients, who also showed lower medication adherence. In the explanatory model, older age (OR 1.02/year), cardiometabolic comorbidities (ORs ~1.2–1.6), highest quartile of morbidity complexity (OR 1.27), polypharmacy (OR 1.34), and concern about medications (OR 1.08) were associated with T2DM, while female sex (OR 0.660), depression (OR 0.888), COPD (0.704), neoplasms (0.688), and higher medication adherence (OR 0.53) were associated with not having T2DM. Conclusions: High-risk chronic patients with T2DM exhibit distinct sociodemographic, functional, and clinical profiles compared with those without T2DM, characterized by greater complexity, cardiometabolic burden, therapeutic intensity and use of healthcare services, supporting the need for tailored, integrated primary health care strategies. Full article

Background: Low-dose computed tomography (LDCT) screening reduces lung cancer mortality; however, the effectiveness of screening programs depends not only on detection, but also on completion of downstream diagnostic pathways following a positive screening result. Refusal of recommended invasive diagnostic procedures represents a critical but understudied form of post-screening attrition. Methods: This retrospective observational study was conducted within an organized multicenter LDCT lung cancer screening program in Vojvodina, Serbia. Consecutive participants screened between September 2020 and October 2025 were included. Positive screening was defined as Lung-RADS 4A, 4B, or 4X. Refusal was defined as the absence of any invasive diagnostic procedure within six months following multidisciplinary team recommendation. Demographic, clinical, smoking-related, and perceptual factors were analyzed. Time to invasive diagnostic procedures was assessed for bronchoscopy and surgical treatment. Multivariable logistic regression was used to identify factors independently associated with refusal. Results: Among 10,261 screened individuals, 479 (4.7%) had positive LDCT findings. Of these, 60 participants (12.5%) refused invasive diagnostic evaluation. In multivariable analysis, multimorbidity (OR 3.45, 95% CI 1.61–7.38), previous malignancy (OR 2.92, 95% CI 1.16–7.35), higher cumulative smoking exposure (OR 1.02 per pack-year, 95% CI 1.00–1.03), and screening center (Subotica vs. Novi Sad: OR 2.40, 95% CI 1.21–4.78) were independently associated with refusal of invasive diagnostic procedures. Greater concern about personal lung cancer risk was associated with a lower likelihood of refusal (OR 0.54, 95% CI 0.29–0.99). Time to bronchoscopy differed significantly across screening centers and screening years, whereas time to surgical treatment was comparable across centers and years. Conclusions: Refusal of invasive diagnostic procedures following positive LDCT screening represents a meaningful implementation challenge influenced by both patient vulnerability and system-level factors. Addressing modifiable barriers through improved risk communication and optimization of post-screening diagnostic pathways may enhance diagnostic continuity and strengthen the real-world effectiveness of lung cancer screening programs. Full article

Background: Transcatheter aortic valve implantation (TAVI) is increasingly used across all risk groups, meaning more patients are living long-term with transcatheter bioprosthetic valves. These patients are often multimorbid and vulnerable to both thrombotic and bleeding complications. Optimal antithrombotic therapy remains uncertain due to differences in trial design, patient demographics, and procedural practices. Methods: We undertook a narrative review that included randomised controlled trials, observational studies, biomarker research, and guideline recommendations on post-TAVI antithrombotic therapy. We evaluated the available evidence for antiplatelet and anticoagulant strategies after TAVI, predictors of bleeding and thrombotic complications, to identify emerging approaches using biomarkers for personalised risk stratification. Results: Thrombotic events after TAVI are predominantly early and procedural in origin, while new-onset atrial fibrillation (AF) leads to substantial late risk. Subclinical leaflet thrombosis is frequent, but its clinical significance remains uncertain, as anticoagulation reduces CT-detected leaflet abnormalities without improving clinical outcomes. Early bleeding within the first 30 days remains a principal contributor to mortality, influenced by frailty, vascular access, comorbidity, and intensity of antithrombotic therapy. Randomised evidence consistently supports a minimalist, indication-driven regimen: single antiplatelet therapy for patients without an oral-anticoagulation (OAC) indication, and OAC monotherapy for those with AF. Routine OAC use in unselected patients carries no advantage and exposes them to harm. Biomarkers and machine-learning models show promise for future individualised risk assessment. Conclusions: Antithrombotic strategies post-TAVI should prioritise minimising bleeding while maintaining adequate thromboembolic protection. Single antiplatelet therapy for patients without an indication for OAC and OAC alone for those with AF offer the best balance of safety and efficacy. Ongoing trials may clarify the role of imaging-guided therapy and biomarker-based risk stratification and refine antithrombotic strategies. Full article

Cognitive impairment is a serious comorbidity in chronic obstructive pulmonary disease (COPD), consistently associated with adverse clinical outcomes, including impaired self-management, poor treatment adherence, reduced participation in pulmonary rehabilitation, and increased risk of mortality. Despite this, it remains inconsistently recognised and insufficiently addressed during routine COPD assessment. This narrative review synthesises current evidence on the recognition and management of cognitive impairment in COPD, with a particular focus on understanding why it continues to be under-recognised and inadequately managed in clinical practice. Across care settings, cognitive concerns are commonly identified informally, assessed selectively, or deferred altogether, even when clinicians acknowledge their relevance to respiratory assessment, treatment implementation, and patient engagement. This persistent evidence–practice gap suggests the influence of factors extending beyond disease- or patient-related explanations alone. Emerging evidence indicates that clinician-level determinants, particularly clinical confidence, play a central role in shaping cognitive care practices. Limited clinical confidence appears to mediate the translation of existing knowledge and competence into clinical action, influencing decisions to initiate assessment, communicate cognitive concerns, assume clinical ownership, and pursue follow-up or referral. These confidence-related barriers are further reinforced by educational limitations, time constraints, diagnostic ambiguity, particularly in the early cognitive impairment stage, and the absence of clear operational guidance within COPD-specific frameworks. Conceptualising cognitive care through the lens of clinical confidence provides a coherent explanation for the underrecognition of cognitive impairment in COPD. It also helps account for observed variability in clinical decision-making, highlighting clinical confidence as a modifiable intermediary between knowledge, competence, and practice and a potential target for strengthening integrated, patient-centred COPD care. Full article

Background/Objectives: Subjective cognitive decline (SCD) is an early stage of dementia, although its risk factors remain unclear. We estimated the prevalence of SCD and its associated dementia risk factors in Brazilian adults. Methods: This cross-sectional study is based on data from the second wave (2019–2021) of the Brazilian longitudinal study of aging (ELSI-Brazil) and a nationally representative sample of adults aged ≥50 years. Prevalence of SCD was estimated and defined as self-reported cognitive decline without objective impairment or dementia diagnosis, and the adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated through logistic regression models. Results: Of 6631 participants, 57.5% were women, and 54.4% were non-white, with a mean age of 65.1 years (standard deviation: ±9.70). SCD prevalence was 19.7% (95% CI 18.6–20.9) for a total of 1346 individuals. Significantly strong positive associations with SCD were observed for sociodemographic factors, particularly lower education (OR = 2.79, 95% CI: 2.02–3.85), as well as older age, non-white ethnicity, and lower income (ORs ranging from 1.50 to 1.79). Lifestyle factors, including loneliness and sedentary behavior, showed moderate associations (OR = 1.33 and 1.35, respectively). Among health-related conditions, multimorbidity was significantly associated with higher odds of SCD (OR = 1.40 for ≥3 chronic diseases), with the strongest association observed for hearing loss (OR = 2.29, 95% CI: 1.93–2.71). Diabetes, visual loss, and depressive symptoms showed more modest significant associations (OR 1.25 to 1.31). Conclusions: Our findings support the prioritization of vulnerable populations in public health strategies aimed at promoting healthy ageing and reducing social and health inequalities. Longitudinal studies are needed to clarify whether modifying associated factors may influence SCD trajectories. Full article