Search Results (673)

Background/Objectives: Appropriate imaging surveillance, established by the Society of Vascular Surgery (SVS), following endovascular aorta repair (EVAR) is critical for patient monitoring. We hypothesized that adherence to follow-up decreases over time, and therefore, the ability to detect endoleaks after EVAR also decreases. Methods: A retrospective cohort study of patients who underwent EVAR from 2014 to 2022 at our institution was completed. Patients were stratified by adherence to SVS guidelines for up to five years postoperatively. Demographics, detection of an endoleak > 30 days postoperatively, distance from our facility, and Area Deprivation Index (ADI) were collected. Comparisons of baseline comorbidities between groups and multivariate logistic regressions were performed using R studio. Results: 395 patients underwent an index EVAR at our institution from 2014–2022. 174 (44%) of patients adhered to all imaging recommendations, with an average loss to follow-up of 9.7% per year. 61 (15.4%) patients had a detected type II endoleak during the study period. Multivariable analysis identified residence > 50 miles from our institution as an independent risk factor for nonadherence (OR 1.76, p = 0.018) when controlling for age, sex, race, and ADI quartile. Conclusions: Adherence to surveillance guidelines gradually decreases after EVAR, but type II endoleak detection continues to occur years following the operation. While residence greater than 50 miles away was associated with nonadherence, patients’ ADI was not. Our results identify an opportunity for providers who may see patients more frequently to assist in reminding and arranging imaging follow-up for patients following their procedure. Full article

Background: Wounds with an avascular component represent a significant challenge in medical care due to impaired blood flow. Synthetic matrices, such as poly-lactic acid (PLA), have demonstrated promising results in promoting wound healing in complex wounds, including those with restricted blood supply, such as diabetic foot and venous leg ulcers. Objective: This case series presents the outcomes of five patients with wounds containing exposure of avascular components, of various etiologies successfully treated with PLA matrices. Case description: Five patients presented complex wounds involving exposure of bone, tendon, fascia, or osteosynthetic material. Wound bed preparation included debridement followed by PLA application covered with additional layers (non-adherent dressing, absorbent dressing, and compression bandage) as needed. Weekly assessments were conducted until full wound closure was achieved. Results: All cases showed successful outcomes, with PLA promoting granulation tissue formation and re-epithelialization, contributing to wound closure. One patient required skin grafts for complete healing. No local infections were reported before or after PLA application. Conclusions: PLA matrices are a practical and effective option for managing complex wounds, promoting tissue regeneration and optimizing wound bed quality for skin grafts or flaps. While these findings are promising, further studies are needed to confirm the broader applicability and efficacy of PLA in the management of wounds containing exposure of avascular structures. Full article

Background/Objectives: The impact of dietary adherence and formula intake regularity on fat-soluble vitamin status in phenylketonuria (PKU) is uncertain. This study assessed whether vitamin A, D, E, and beta-carotene levels differ by dietary adherence and regularity of Phe-free formula intake. Methods: A cross-sectional study included 98 individuals (age 6–41 years) with vitamin D measurements. In a subgroup of 68 patients, vitamin A, vitamin E, and beta-carotene levels were determined. Vitamin levels were compared between adherent and non-adherent groups and between participants with regular vs. irregular formula intake. A subsequent systematic review and meta-analysis of six studies (from PubMed, Scopus, Web of Science, and Cochrane; searched in August 2025) pooled standardised mean differences (SMDs) using fixed-effects and random-effects models. Results: The cross-sectional results showed higher vitamin D in adherent (35.60 [30.39–41.65] vs. 32.90 [26.50–40.00] ng/mL, p = 0.034) and regular formula consumers (35.97 [30.03–42.28] vs. 30.20 [26.08–35.06] ng/mL, p = 0.002). Beta-carotene was elevated with regular intake (74.40 [56.70–98.45] vs. 53.20 [34.10–68.60] ng/mL, p = 0.003). Meta-analysis confirmed higher vitamin D in adherent individuals (fixed-effects model, SMD = 0.290, 95% CI: 0.004, 0.576, p = 0.047) and regular consumers (fixed-effects model, SMD = 0.750, 95% CI: 0.382, 1.118, p < 0.0001). No differences were observed for vitamin E or beta-carotene. Conclusions: Adherence to diet and regular formula intake is associated with improved vitamin D status, underscoring the critical role of fortified formulas in PKU management. The very low certainty of evidence necessitates further research, especially for the other fat-soluble vitamins. Nonetheless, clinical practice should emphasise support for adherence and ongoing nutritional monitoring. Full article

Background/Objectives: Ulcerative colitis (UC), a chronic inflammatory bowel disease, affects approximately 5 million individuals worldwide, exerting a considerable influence on global health and economic systems. Among the challenges in UC management, treatment non-adherence stands out as a critical issue, often compromising therapeutic efficacy. One strategy to address this challenge is by reducing pill burden, which may improve patient compliance and optimize treatment outcomes. Methods: This randomized, two-sequence, four-period, crossover replicate study evaluated the pharmacokinetic profiles, bioequivalence, and safety of a newly developed 1500 mg mesalazine gastro-resistant tablet compared to three of the reference 500 mg Claversal^® gastro-resistant tablets (total dose 1500 mg) in 80 healthy participants under fasted conditions. Results: Bioequivalence between mesalazine formulations was observed in both the rate and extent of systemic bioavailability. The geometric mean ratios and their 90% CI were 102.51% (95.85–109.63) for AUC_0–∞, 103.36% (96.40–110.83) for AUC_0–t, 84.49% (78.24–91.24) for AUC_8–48h, and 114.24% (100.15–130.32) for C_max. All within the accepted bioequivalence ranges, confirming comparable pharmacokinetic performance. Secondary pharmacokinetic parameters such as t_max, t_1/2, K_e, Cl, and MRT were also consistent across both formulations. The incidence of adverse events was comparable between the two mesalazine formulations, with only flatulence and mild self-limited rash considered possibly related to test treatment. Conclusions: Overall, the 1500 mg formulation demonstrated a pharmacokinetic profile and tolerability comparable to the reference formulation, offering a higher-strength option to reduce daily pill burden. This strategy is of clinical relevance, particularly for improving treatment adherence among UC patients who need to take multiple pills daily to achieve their required dosage. While adherence is influenced by various factors, reducing pill burden may facilitate compliance and optimize therapeutic efficacy. Full article

Background/Objectives: Medication non-adherence and incomplete seizure documentation remain major challenges in epilepsy care, particularly in drug-resistant forms. Digital health tools may improve self-management by integrating seizure tracking, adherence support, and patient–clinician communication. This narrative review summarizes current mobile applications for seizure monitoring and adherence and outlines opportunities and gaps in clinical translation. Methods: A narrative synthesis (PubMed, Scopus, Google Scholar; 2019–2025; English) summarized functionality, usability, clinical validation, and limitations of epilepsy-focused mobile/wearable applications; no systematic methods or meta-analysis were applied. Results: Existing tools cluster into seizure diary apps, smartwatch-based monitoring systems, and adherence-focused applications. While they improve documentation and treatment regularity, most lack adaptive personalization, language localization and therapeutically active components. Comprehensive platforms combining tracking, adherence analytics and telehealth remain unevenly validated. Validated wearable detectors for generalized tonic–clonic seizures typically report sensitivity in the 80–95% range in real-world or simulated-real-world studies, alongside variable specificity and false-alarm rates, underscoring the need for individualized deployment and calibration. Conclusions: Mobile and wearable applications are promising adjuncts to routine epilepsy care. The field is gradually shifting from passive monitoring toward integrated, user-centered platforms that blend monitoring, predictive analytics and neuromodulation. This review also briefly outlines a conceptual example of an integrated mobile platform that combines seizure documentation, adherence support and patient-initiated rhythmic cueing; this example is presented at a purely exploratory level and requires further clinical validation. Full article

Tuberculosis is a serious public health issue. It is the most prevalent cause of death from a single infectious agent and globally, it is among the top 10 causes. One of the most crucial strategies to combat the TB pandemic is to administer basic anti-TB treatment for at least six months. However, the long duration of TB therapy raised the issue of non-adherence, which negatively impacted the clinical and public health outcomes of TB treatment. As a result, directly observed therapy has been used as a standard method to encourage adherence to anti-TB medication. However, this strategy has been challenged because of the difficulty, stigma, decreased economic output, and decreased quality of life, all of which might eventually make adherence problems worse. Furthermore, there is disagreement regarding the efficacy of the directly observed treatment (DOT) strategy in enhancing anti-TB adherence. Digital technology might therefore be a key tool to enhance DOT implementation. The World Health Organization Multidimensional Adherence Model (WHO-MAM) may be used with digital technologies to further improve drug adherence and change behavior. Aim: This paper aimed at reviewing the latest evidence on TB drug non-adherence, its contributing factors, the efficacy of DOT and its alternatives, and the use of digital technologies and WHO-MAM to improve medication adherence. This report analyzed linked publications using a narrative review process to address the study goals. Conventional DOT has several drawbacks when it comes to TB therapy. Medication adherence may be enhanced by incorporating WHO-MAM into the creation of digital technologies. To address several challenges associated with DOT implementation, digital technology offers a chance to enhance drug adherence. Full article

Background: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased morbidity and mortality. Continuous positive airway pressure (CPAP) remains the first-line therapy, but its long-term effectiveness is limited by suboptimal adherence, with only 50–60% of patients achieving the recommended use. Evidence on adherence with alternative modalities, such as bilevel positive airway pressure (BiPAP) or oxygen therapy, is even more limited. Furthermore, few studies have directly compared these treatments with each other, particularly in relation to survival outcomes. Objective: Evaluate 5-year survival in patients with OSA treated with CPAP, BIPAP, or oxygen therapy. Methods: A retrospective cohort study with survival analysis was conducted in subjects with OSA followed at a tertiary-level institution in Colombia between January 2005 and December 2021. Results: Among 3039 patients with OSA (mean age 59.6 years; 59.8% male), the five-year mortality rate was 5.8%. Deceased patients presented a higher prevalence of comorbidities, including hypertension, diabetes, and cardiovascular disease (all p < 0.001). Adherence to CPAP was significantly lower in deceased patients. Survival analysis showed the highest five-year survival among adherent CPAP/Auto-CPAP users (95.6%), followed by non-adherent CPAP (95%) and adherent BiPAP users (94.1%). Lower survival was observed in non-adherent BiPAP users (91.7%) and oxygen therapy patients (80.6%). In multivariable analysis, treatment type, older age, congestive heart failure, chronic lung disease, and metastatic cancer were independently associated with increased mortality risk. Conclusions: Five-year survival in patients with obstructive sleep apnea was significantly associated with the treatment modality and adherence level. Full article

Lactarius deliciosus is a widely distributed edible mushroom valued as a functional food due to its rich content of nutrients, phenolic compounds, and flavonoids, which contribute to its strong antioxidant and antimicrobial properties. The present study aimed to optimize a green microwave-assisted extraction method for maximal recovery of bioactive phenolic compounds from Lactarius deliciosus extract (LDE) and to evaluate its antioxidant, antiproliferative, antimetastatic, and anti-inflammatory effects on human colon carcinoma (Caco-2) cells. The study demonstrated that solvent polarity and composition critically influence the recovery of antioxidant biomolecules, identifying water and NaDES 1 (glycerol/glycine/water) as the most efficient and sustainable solvents for microwave-assisted extraction at 225 °C. The LDE showed high levels of phenolic compounds—particularly 4-hydroxybenzoic and vanillic acids—indicating potent antioxidant potential and possible anticancer efficacy. The results revealed that the LDE significantly reduced colony formation and cell adhesion in a dose-dependent manner, leading to nearly complete inhibition of clonogenic survival at the IC₅₀ concentration and a marked increase in cell death among non-adherent colon cancer cells. In addition, LDE inhibited the proliferation of Caco-2 cells by inducing G0/G1 cell cycle arrest and apoptosis, associated with altered mitochondrial potential and increased caspase-3 activity. The LDE modified the redox balance of the cell by decreasing the ROS levels and exerts anti-inflammatory effects through significant downregulation of NOS2 expression, without adversely affecting the intestinal barrier. The study concludes that LDE bioactive compounds show strong promise as anticancer and functional ingredients, demonstrating antioxidant, antiproliferative, antimetastatic, and anti-inflammatory effects. Full article

Background/Objectives: Protein-energy wasting (PEW) affects up to 75% of hemodialysis (HD) patients, yet adherence to oral nutritional supplements (ONSs) remains poorly understood. This study evaluated ONS adherence patterns, associated socio-demographic and psychological factors, and clinical outcomes over 24 months in chronic HD patients. Methods: A 24-month prospective study was conducted in 101 HD patients. Adherence was assessed using the 4-item Morisky Medication Adherence Scale (MMAS-4), and depressive symptoms with the Beck Depression Inventory (BDI). Nutritional status was evaluated using the Malnutrition–Inflammation Score (MIS) and anthropometric measurements. Laboratory markers were obtained. Individualized nutritional education was provided at each visit. Results: Regular ONS use was reported in 50.5% of patients. High adherence (MMAS-4 = 0) was observed in 36.6% of the cohort. Forgetfulness (45.3%) and adverse effects (34.4%) were the most common obstacles. Adherence was significantly associated with sex (p = 0.007), with men more frequently demonstrating low adherence. Education level showed a weak, but significant positive correlation with MMAS-4 score (Spearman’s ρ = 0.25, p = 0.018), indicating slightly lower adherence among more educated patients. MMAS-4 and BDI scores were positively correlated (Spearman’s ρ = 0.25, p = 0.04), indicating that greater depressive symptom burden was associated with lower adherence. Regular ONS users demonstrated improved nutritional status (lower MIS; 9 vs. 7, p < 0.001), higher hemoglobin (106 vs. 114 g/L, p = 0.03), and increased mid-upper arm circumference (MUAC; 26 vs. 28 cm, p = 0.02). Lean tissue mass was preserved over time (p = 0.009). However, individualized education had limited effect on patients with initially low adherence. Individualized nutritional education was associated with improved acceptance and implementation of recommendations. Over two years of follow-up, nutritional education was associated with preserved lean and fat tissue index (LTI, p = 0.009; FTI, p = 0.08), reductions in interdialytic weight gain, and significant improvements in MUAC, waist circumference, and scapular skinfold thickness (p = 0.03; p < 0.001; p = 0.02). Prealbumin and hemoglobin levels also increased significantly (p = 0.02; p = 0.04). However, education alone was insufficient for certain subgroups, particularly older patients and those initially classified as non-adherent. During follow-up, 17 patients died. Lower MUAC (OR = 2.97, 95% CI: 1.45–6.08) and triceps skinfold thickness (OR = 1.37, 95% CI: 1.12–1.68) were the strongest independent predictors of mortality. Conclusions: Adherence to ONSs remains suboptimal in HD patients. Individualized nutritional education was associated with improved adherence and nutritional status in some subgroups but may be insufficient in older or initially non-adherent patients. Simple anthropometric markers are strong mortality predictors and may offer practical value for routine monitoring. Full article

Background/Objectives: Despite the availability of highly effective medications, hypertension is among the most important risk factors for mortality. Because medication adherence is challenging worldwide, enhancing it to improve the prognosis of hypertension is useful. The aim of this study was to describe the prevalence of antihypertensive medication nonadherence among individuals aged 18–64 years in a deprived Hungarian population and its determinant factors, and to quantify the impact of antihypertensive medication nonadherence on premature mortality. Methods: We used data from a cohort of hypertensive individuals aged 18–64 years linked to the Health Insurance Fund’s medication purchasing data. The antihypertensive treatment adherence appropriateness (ATAP) was computed as the ratio of the observed time when a patient was properly treated to their observed survival time. ATAP was dichotomized by an observed mean of 0.872. Using adjusted odds ratios (AORs) from multivariate logistic regression models with 95% confidence intervals (CIs), we analyzed the factors influencing the mortality risk in 4962 participants over seven years of follow-up. Results: A total of 493 deaths occurred. An extremely high mortality risk was observed among patients with inappropriate adherence (AOR = 56.2, 95%CI: 41.9–75.4), which could be attributed partly to residual confounding. Significant protective factors were female sex and high education attainment. However, older age and all investigated comorbidities (diabetes mellitus, ischemic heart disease, chronic obstructive pulmonary disease, and cancer) were significantly associated with an increased risk of a lethal outcome. Similarly, smoking was also a risk factor. Conclusions: Our investigation revealed the following: (1) in the studied group of patients aged 18–64 years from an extremely disadvantaged Hungarian population, 87.2% of the person-time was covered by the appropriate redemption of medications; (2) nonadherence to medication was more common among younger adults, men, Roma people, current smokers, and COPD patients, whereas the likelihood of appropriate adherence was higher among patients with diabetes mellitus; (3) medication nonadherence was an extremely strong risk factor for a lethal outcome of HTN during the 7-year follow-up period; and (4) methods by which nonadherent patient behavior can be detected should be applied rigorously, and the detected nonadherence should be considered a signal for intervention to improve the prognosis of HTN. Full article

Bioengineered dermal–epidermal composites (DECs) have demonstrated promise initiating skin regeneration and hair follicle neogenesis after injury. DECs in our work comprise a collagen matrix embedded with human dermal papilla cells (HDPCs) overlaid with human keratinocytes. HDPCs, as three-dimensional spheroids, enhance hair follicle formation, working in tandem with keratinocytes. Herein, 3D printed stamped PDMS microwell arrays were used as a strategy for spatially patterning dermal papilla spheroids in the dermal components of the DEC. DECs were transferred to cell culture media for 5 days followed by air–liquid interface culture for 2 days. Spheroid diameter, cell viability, and qPCR gene expression analyses were conducted. DECs were surgically grafted on immunocompromised mice, and healing was followed for 10 weeks. HDPCs cultured in the microwell arrays formed patterned viable spheroids and successfully transferred to the collagen dermal matrix. RNA analysis using qPCR showed upregulation of key HDPC markers (VCAN and BMP6) in DC microwell patterned HDPC spheroids compared to monolayers. This work represents a novel 3D printing strategy optimizing designing patterned HDPC spheroids in the extracellular matrix to regenerate functional human skin instead of scar tissue after injury. Full article

Background: The purpose of this study was to assess differences in clinical symptoms and signs of DED in non-adherent to treatment patients to describe long-term disease progression. Methods: 120 patients previously diagnosed with Dry Eye Disease (DED) were contacted to undergo a second eye examination. The final included participants were classified into three groups based on when the second examination was scheduled: 4 years (Group 1; n = 33), 6 years (Group 2; n = 18) or 8 years (Group 3; n = 37) since the diagnostic visit. All included participants were classified as ‘non-adherent to DED treatment’, defined as patients who reported not following their prescribed DED therapy. In both examinations, Ocular Surface Disease Index (OSDI) questionnaire, tear film osmolarity, inter-eye osmolarity (osmolarity |OD-OS|), Fluorescein Break-Up Time (FBUT), Maximum Blink Interval (MBI) and corneal staining were evaluated. Results: OSDI score improved after 4 years of DED diagnosis (Group 1, mean difference close to 12 points, p < 0.001) and after 8 years (Group 3, mean difference of 9 points, p < 0.001), but remained stable after 6 years (Group 2, p = 0.328). Osmolarity worsened only after 6 years of DED diagnosis (Group 2, mean difference of 13.2 mOsm/L, p = 0.011), while osmolarity |OD–OS| showed no change (all p ≥ 0.231). FBUT values were stable across all groups (all p ≥ 0.265). MBI increased after 4 and 8 years of DED diagnosis (Groups 1 and 3, p ≤ 0.003), but not after 6 years (Group 2, p = 0.391). Corneal staining worsened after 8 years of DED diagnosis (Group 3, 0.55 points, p = 0.011), with no changes at 4 or 6 years (Groups 1 and 2, both p ≥ 0.318). Conclusions: In non-adherent DED patients, osmolarity |OD-OS| and tear film stability remain stable during the natural course of the disease, while ocular surface damage increases. However, the subjective symptomatology and the nociceptive blink reflex due to ocular discomfort decreased since the diagnostic visit. Full article

Background and Objectives: Breast cancer is the most common cancer in women, with approximately 80% being oestrogen receptor positive, necessitating adjuvant endocrine therapy (AET) to reduce recurrence. Treatment adherence is crucial, yet 10–50% of patients take incorrect doses or discontinue therapy, which is associated with a 20% increase in mortality. AET may also impact bone health. This study aimed to explore patients’ beliefs about endocrine treatment, investigate how perceptions of medication risk and benefit affect adherence, and assess changes in bone mineral density (BMD) during therapy. Materials and Methods: A cross-sectional mixed-method study was conducted. One hundred patients diagnosed with oestrogen receptor-positive breast cancer in 2020 were sent the Beliefs about Medicines Questionnaire–Adjuvant Endocrine Therapy (BMQ-AET) and 101 semi-structured telephone interviews were completed. Initial and most recent Dual-Energy X-ray Absorptiometry (DEXA) scans were compared to assess changes in BMD. Results: The questionnaire response rate was 55% (n = 55). Forty-nine patients returned the postal paper survey and six patients responded via QR code. One hundred and one patients participated in semi-structured telephone interviews. Of the total cohort, 91.7% were adherent to AET, while 13 patients (8.3%) were non-adherent. Non-adherent patients had significantly lower BMQ-AET Necessity scores (mean 12.08 vs. 19.22; median 12 vs. 20; p < 0.001) and higher Concerns scores (mean 17 vs. 13.46; Median 17 vs. 13; p = 0.002). The most common reasons for non-adherence were joint pain and reduced quality of life (58%), highlighting a need for additional support in managing side effects. Among the participants with suitable DEXA data, the majority (54.2%) demonstrated an increase in BMD over time. Conclusions: This study demonstrates high adherence to AET, with non-adherent patients showing lower perceived necessity and greater concern about treatment. These findings emphasise the importance of addressing patient beliefs to enhance adherence. The observed improvements in BMD suggest that proactive bone health management, alongside AET, may mitigate expected declines, challenging conventional assumptions regarding therapy-related bone loss. Full article

Introduction: Cardiovascular disease (CVD) remains a primary cause of mortality worldwide, with persistent geographic disparities driven by a complex interplay of risk factors. Continual updates of localized variations in CVD mortality are essential to develop targeted interventions for optimizing disease and healthcare management. Methods: This study investigated associations between CVD mortality and a comprehensive set of biological, environmental, behavioral, and socioeconomic factors across all U.S. counties, employing correlation, geospatial visualization, stepwise multiple regression, and machine learning models to evaluate the importance of risk associations. Results: Significant disparities in CVD mortality trend were observed across race, age, sex, and region, with elevated rates among older adults, men, and Blacks, particularly in southeastern states exhibiting severe social vulnerability. Correlation analysis identified disease management (e.g., COPD, hypertension, medication non-adherence), environmental factors (PM2.5), lifestyle behaviors (e.g., smoking, sleep duration), and socioeconomic status (e.g., poverty, single-parent households, education) as important contributors to CVD mortality. Conversely, higher household income, physical activity, and cardiac rehabilitation participation were strong protectors. Multiple regression explained 66.9% variance in CVD mortality, recognizing PM2.5, smoking, and medication non-adherence as top associated factors. Random Forest models underscored COPD’s predictive dominance, followed by medication non-adherence, smoking, and sleep duration. Conclusions: The findings highlight the geospatial connection of risk factors to CVD mortality disparities across U.S. counties. They emphasize the critical importance of data-driven strategies targeting air quality, tobacco control, social inequities, and chronic disease management to mitigate CVD burden and promote health equity. Full article

Statins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well-tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated in the development of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates the transcription of TOMM40 and TOMM22, genes that encode major subunits of the translocase of the outer mitochondrial membrane (TOM) complex. Mitochondrial effects of knockdown of TOMM40 and TOMM22 in mouse C2C12 and primary human skeletal cell myotubes include impaired oxidative function, increased superoxide production, reduced cholesterol and CoQ levels, and disrupted markers of mitochondrial dynamics and morphology as well as increased mitophagy, with similar effects resulting from simvastatin exposure. Overexpression of TOMM40 and TOMM22 in simvastatin-treated mouse and human skeletal muscle cells rescued effects on markers of mitochondrial dynamics and morphology, but not oxidative function or cholesterol and CoQ levels. These results show that TOMM40 and TOMM22 have key roles in maintaining both mitochondrial dynamics and function and indicate that their downregulation by statin treatment results in mitochondrial effects that may contribute to statin-induced myopathy. Full article