Search Results (10,366)

Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene–environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue. Full article

Background/Objectives: Cognitive impairment in older adults has emerged as a growing public health concern, particularly in relation to COVID-19 infection and its associated neuropsychiatric symptoms. The identification of modifiable risk factors may contribute to the development of targeted preventive strategies. This study aimed to assess predictors of cognitive impairment in older adults with and without recent SARS-CoV-2 infection. Methods: A prospective cohort study was conducted from June 2023 to March 2024 at a tertiary hospital in western Mexico. Adults aged 65 years or older with confirmed SARS-CoV-2 infection within the previous six months, along with uninfected controls, were enrolled. Cognitive function (Mini-Mental State Examination), depression (PHQ-9), anxiety (Geriatric Anxiety Inventory), insomnia (Insomnia Severity Index), functional status (Katz Index and Lawton–Brody Scale), and laboratory markers were evaluated at baseline, three months, and six months. The primary outcome was cognitive impairment at six months. Independent predictors were identified using a multivariable generalized linear mixed-effects model. Results: Among the 111 participants, 20 (18.8%) developed cognitive impairment within six months. Low serum magnesium (adjusted risk ratio [aRR] 2.73; 95% CI 1.04–7.17; p = 0.041) and depression (aRR 5.57; 95% CI 1.88–16.48; p = 0.002) were independently associated with a higher risk. A significant synergistic among COVID-19, depression, and hypomagnesemia was observed (RR 44.30; 95% CI 9.52–206.21; p < 0.001), corresponding to the group with simultaneous presence of all three factors compared to the group with none. Conclusions: Depression and hypomagnesemia appear to be independent predictors of cognitive impairment in older adults with recent COVID-19 infection. These findings suggest potential targets for prevention and support the implementation of routine neuropsychiatric and biochemical assessments in this population. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

Study Design: Prospective observational study. Background: Lumbar spinal stenosis (LSS) impairs balance and gait function, increasing fall risk and limiting quality of life. Although postoperative recovery of balance is clinically important, longitudinal data using multidimensional balance assessments are limited. Methods: A prospective cohort study was conducted in 101 patients (mean age 74.9 ± 6.9 years) undergoing surgery for LSS. The Brief Balance Evaluation Systems Test (Brief BESTest), Oswestry Disability Index (ODI), Modified Falls Efficacy Scale (MFES), Zurich Claudication Questionnaire (ZCQ), and Visual Analog Scales (VAS) for pain/numbness were evaluated preoperatively and at 6 and 12 months postoperatively. Changes over time and correlations between Brief BESTest and PROMs were analyzed. Results: The total Brief BESTest score significantly improved from 13.3 ± 5.3 preoperatively to 16.1 ± 5.1 at 6 months and 16.0 ± 5.1 at 12 months (p < 0.01). Subdomains including Anticipatory Adjustments, Postural Responses, Sensory Orientation, and Stability in Gait improved significantly, while Stability Limits did not. At 12 months postoperatively, ODI decreased by 19.1%, ZCQ symptom and function scores improved by 0.8 and 0.9 points, respectively, and VAS scores improved by 17.1 mm for low back pain, 26.5 mm for lower limb pain, and 19.5 mm for numbness, all showing marked improvements from baseline. MFES also increased significantly postoperatively. The Brief BESTest score correlated significantly with MFES and ZCQ-PFS at baseline, and with ODI, ZCQ, and VAS scores at 12 months. Conclusions: Balance ability in LSS patients improved after surgery, as measured by the Brief BESTest, with clinically meaningful changes maintained for 12 months. Improvements in balance were significantly associated with reductions in pain, disability, and fear of falling, suggesting the Brief BESTest is a comprehensive indicator of postoperative recovery. Full article

Coffee is one of the most widely consumed beverages globally, with over 60% of Americans drinking it daily. This review examines coffee’s multifaceted impact on health and well-being, drawing on decades of research. Overall, the consensus is that moderate coffee intake is more beneficial than harmful across a wide range of health outcomes. Numerous large-scale, prospective cohort studies from around the world have consistently shown that moderate coffee consumption—typically three to five cups per day—is associated with reduced overall mortality and lower risk of major diseases such as cardiovascular diseases, diabetes, stroke, respiratory conditions, cognitive decline, and potentially several types of cancer, including liver and uterine cancers. Both caffeinated and decaffeinated coffee have shown benefits. The addition of sugar and cream to coffee may attenuate coffee’s positive health effects. Despite historical concerns, coffee consumption is not linked to increased risks of cancer, hypertension, or arrhythmia. However, some concerns remain. For pregnant women, coffee consumption should be limited to lower amounts, such that the daily intake of caffeine does not exceed 200 mg/day. Also, excessive caffeinated coffee intake may cause anxiety or sleep disturbances. Coffee’s health-promoting mechanisms include improved glucose balancing, increased physical activity, increased fat oxidation, improved lung function, and reduced inflammation. Beyond mortality and chronic diseases, coffee consumption affects many aspects of well-being: it supports hydration, boosts mental acuity, enhances physical performance, and may aid bowel recovery after surgery. While the field is well-studied via long-term observational cohorts, future research should focus on randomized controlled trials, Mendelian randomization studies, and granular analyses of coffee types and additives. Full article

Background/Objectives: Adult Spinal Deformity (ASD) is a pathologic malalignment of the spine that can lead to significant reductions in quality of life, functional limitations, and increased morbidity. While poor mental health is commonly observed among patients undergoing ASD surgery, its impact on surgical outcomes remains poorly understood. We conducted a systematic review and meta-analysis to examine the association between preoperative mental health and outcomes following surgical correction for ASD. Methods: A comprehensive search of MEDLINE, Embase, Web of Science, and Scopus was performed from inception to April 2025 to identify studies investigating the relationship between preoperative mental health and postoperative health-related quality of life outcomes or complications. Data was pooled using a restricted maximum likelihood (REML) random-effects model. Heterogeneity was assessed using Cochran’s Q statistic, and between-study variance was reported as τ². Study quality was assessed with the Newcastle–Ottawa Scale, and risk of bias was evaluated using the ROBINS-I tool. Results: Twenty-four studies comprising a total of 248,427 patients met inclusion criteria. In pooled analyses, patients with poor preoperative mental health showed comparable improvements in health-related quality of life measures after surgery (standardized mean difference [SMD] −0.04, 95% CI −0.30 to 0.22; I² = 91.5%, τ² = 0.42) and in pain scores (SMD −0.15, 95% CI −0.42 to 0.11; I² = 71.8%, τ² = 0.09). However, patients with poor mental health had significantly higher odds of postoperative complications (odds ratio [OR] 1.44, 95% CI 1.23 to 1.67; I² = 97.4%, τ² = 0.08). These patients also demonstrated worse preoperative disease severity (SMD –0.94, 95% CI −1.41 to −0.47; I² = 95.5%, τ² = 1.64) and worse postoperative disease severity (SMD –0.34, 95% CI −0.44 to −0.25; I² = 48.9%, τ² = 0.03). Conclusions: While patients with poor preoperative mental health have a greater disease severity both before and after ASD surgery, they appear to experience comparable benefits from surgical intervention compared to those without. Recognizing and managing mental health may be useful in preoperative management of ASD patients. Further prospective studies to further elucidate these associations are necessary. Full article

The green renovation of existing residential buildings is a key way for the construction industry to achieve sustainable development and the dual carbon goals of China, which makes it urgent to make collaborative decisions among multiple stakeholders. However, because of divergent interests and risk perceptions among governments, energy service companies (ESCOs), and owners, the implementation of green renovation is hindered by numerous obstacles. In this study, we integrated prospect theory and evolutionary game theory by incorporating core prospect-theory parameters such as loss aversion and perceived value sensitivity, and developed a psychologically informed tripartite evolutionary game model. The objective was to provide a theoretical foundation and analytical framework for collaborative governance among stakeholders. Numerical simulations were conducted to validate the model’s effectiveness and explore how government regulation intensity, subsidy policies, market competition, and individual psychological factors influence the system’s evolutionary dynamics. The findings indicate that (1) government regulation and subsidy policies play central guiding roles in the early stages of green renovation, but the effectiveness has clear limitations; (2) ESCOs are most sensitive to policy incentives and market competition, and moderately increasing their risk costs can effectively deter opportunistic behavior associated with low-quality renovation; (3) owners’ willingness to participate is primarily influenced by expected returns and perceived renovation risks, while economic incentives alone have limited impact; and (4) the evolutionary outcomes are highly sensitive to parameters from prospect theory, The system’s evolutionary outcomes are highly sensitive to prospect theory parameters. High levels of loss aversion (λ) and loss sensitivity (β) tend to drive the system into a suboptimal equilibrium characterized by insufficient demand, while high gain sensitivity (α) serves as a key driving force for the system’s evolution toward the ideal equilibrium. This study offers theoretical support for optimizing green renovation policies for existing residential buildings in China and provides practical recommendations for improving market competition mechanisms, thereby promoting the healthy development of the green renovation market. Full article

Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical stress on adjacent or opposing teeth. This study aimed to investigate the association between the increased number of dental implants and the incidence of cracked teeth following the introduction of implant insurance. Methods: A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul St. Mary’s Dental Hospital. Patients who underwent molar crown restorations between 2014 and 2022 were included. The incidence and clinical features of cracked teeth were compared before (2014–2015) and after (2016–2022) the introduction of implant insurance. Statistical analyses assessed differences in symptom presentation, pulp status, and treatment outcomes. Results: Among 5044 molars restored with crowns, 1692 were diagnosed with cracks. The incidence of cracked teeth significantly increased after NHI coverage for implants (25.5% vs. 32.6%, p < 0.001). Cases after insurance implementation showed fewer signs and symptoms at initial presentation (67.4% vs. 50.0%, p < 0.001), reduced irreversible pulpitis (37.2% vs. 25.8%, p < 0.001), and increased preservation of pulp vitality (46.9% vs. 57.8%, p < 0.001). These shifts may reflect changes in occlusal adjustment practices and earlier clinical intervention. Conclusions: The findings suggest a temporal link between increased implant placement and the rising incidence of cracked teeth. Implant-induced occlusal changes may contribute to this trend. Careful occlusal evaluation and follow-up are essential after implant placement, and further prospective studies are warranted to confirm causality and refine prevention strategies. Full article

Background/Objectives: Historically, echocardiographic imaging of the right heart has been challenging because its abnormal geometry is not conducive to reproducible anatomical and functional assessment. With the development of advanced echocardiographic techniques, it is now possible to complete an integrated assessment of the right heart that has fewer assumptions, resulting in increased accuracy and precision. Echocardiography continues to be the first-line imaging modality for diagnostic analysis and the management of acute and chronic right heart failure because of its portability, versatility, and affordability compared to cardiac computed tomography, magnetic resonance imaging, nuclear scintigraphy, and positron emission tomography. Virtually all echocardiographic parameters have been well-validated and have demonstrated prognostic significance. The goal of this narrative review of the echocardiographic parameters of the right heart chambers and hemodynamic alterations associated with right ventricular dysfunction is to present information that must be acquired during each examination to deliver a comprehensive assessment of the right heart and to discuss their clinical significance in right heart failure. Methods: Using a literature search in the PubMed database from 1985 to 2025 and the Cochrane database, which included but was not limited to terminology that are descriptive of right heart anatomy and function, disease states involving acute and chronic right heart failure and pulmonary hypertension, and the application of conventional and advanced echocardiographic modalities that strive to elucidate the pathophysiology of right heart failure, we reviewed randomized control trials, observational retrospective and prospective cohort studies, societal guidelines, and systematic review articles. Conclusions: In addition to the conventional 2-dimensional echocardiography and color, spectral, and tissue Doppler measurements, a contemporary echocardiographic assessment of a patient with suspected or proven right heart failure must include 3-dimensional echocardiographic-derived measurements, speckle-tracking echocardiography strain analysis, and hemodynamics parameters to not only characterize the right heart anatomy but to also determine the underlying pathophysiology of right heart failure. Complete and point-of-care echocardiography is available in virtually all clinical settings for routine care, but this imaging tool is particularly indispensable in the emergency department, intensive care units, and operating room, where it can provide an immediate assessment of right ventricular function and associated hemodynamic changes to assist with real-time management decisions. Full article

Background/Objectives: Vitamin D testing has increased significantly in developed countries in recent decades. We aimed to describe trends in vitamin D testing rates and factors associated with testing and vitamin D deficiency in Queensland, Australia (2011–2019). Methods: We used data from the QSkin Sun and Health Study (n = 40,417), a prospective population-based cohort study with linkage to the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme, and pathology laboratories. Main outcomes included age-standardized incidence rate of vitamin D testing; having ≥1 vitamin D test during follow-up; vitamin D deficiency (25-hydroxyvitamin D concentration <50 nmol/L) in the first vitamin D test; and repeat vitamin D tests. Results: The age-standardized incidence rate of testing increased by 2% per quarter during follow-up. Of the 35,250 participants analyzed for associations with testing (median age of 57 years, 52% female), 45% had ≥1 vitamin D test. Among those tested, 56% had no apparent clinical indication for their initial vitamin D test, 21% were vitamin D deficient in their initial test, and 58% had a repeat test. Repeat testing occurred in 56% who were not deficient in their prior test, while only two-thirds of those deficient received a follow-up assessment. Participants who visited a general practitioner ≥2 times in the year prior to follow-up were 60% more likely to have ≥1 vitamin D test compared with those with no visit, but general practitioner (GP) visits were not associated with risk of vitamin D deficiency. Conclusions: These results suggest that initiatives are needed to help clinicians target vitamin D testing in alignment with clinical guidelines. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with disrupted lipid metabolism. This study aimed to uncover novel molecular subtypes and biomarkers by integrating sphingolipid metabolism-related genes (SMGs) with machine learning approaches. Using data from the GEO and GeneCards databases, 29 UC-related SMGs were identified. Consensus clustering was employed to define distinct molecular subtypes of UC, and a diagnostic model was developed through various machine learning algorithms. Further analyses—including functional enrichment, transcription factor prediction, single-cell localization, potential drug screening, molecular docking, and molecular dynamics simulations—were conducted to investigate the underlying mechanisms and therapeutic prospects of the identified genes in UC. The analysis revealed two molecular subtypes of UC: C1 (metabolically dysregulated) and C2 (immune-enriched). A diagnostic model based on three key genes demonstrated high accuracy in both the training and validation cohorts. Moreover, the transcription factor FOXA2 was predicted to regulate the expression of all three genes simultaneously. Notably, mebendazole and NVP-TAE226 emerged as promising therapeutic agents for UC. In conclusion, SMGs are integral to UC molecular subtyping and immune microenvironment modulation, presenting a novel framework for precision diagnosis and targeted treatment of UC. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro^® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article

This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in IBD were also explored. A total of 86 UC patients, 68 CD patients, and 41 healthy controls were prospectively enrolled from four Norwegian hospitals (2013–2022). Diagnosis and disease activity were established using standard clinical, endoscopic, and biomarker criteria. Serum samples were analyzed for total Ig, IgG, IgM, IgA, and IgE antibodies against A. simplex and Pseudoterranova decipiens using ELISA. Anti-A. simplex IgG seroprevalence was 4.9% in controls and 3.2% in IBD (3.5% UC, 2.9% CD). IgM seroprevalence was 0% in all groups. IgA seroprevalence was higher in IBD (16.2%) than controls (4.9%), with 14.0% in UC and 19.1% in CD. IgE seroprevalence was low across all groups. Smoking correlated with lower antibody levels and higher surgery rates. In UC, higher anti-A. simplex IgG and IgE levels were associated with milder disease and better prognosis. Anti-TNFα and azathioprine treatments were linked to higher anti-A. simplex IgA. Norwegian UC and CD patients had significantly higher anti-A. simplex total Ig and IgA seroprevalence than healthy controls, indicating increased exposure or immune response. Anti-A. simplex IgG and IgE may serve as markers of clinical activity in UC. Further research is warranted to clarify the clinical significance of these findings. Full article

Background: High-sensitivity cardiac troponin (hs-cTn) is useful for detecting acute myocardial infarction, but chronic hemodialysis patients often have elevated baseline levels that exceed the upper reference limit (URL). This study aimed to determine whether hs-cTnI levels in asymptomatic hemodialysis patients exceed the URL established for the general population, evaluate the impact of high-flux hemodialysis on hs-cTnI concentrations, and examine associations between hs-cTnI levels and subsequent hospitalization or mortality. Methods: A prospective, single-center cohort study was conducted at a tertiary care center from August 2023 to July 2024. Blood samples for hs-cTnI were collected from asymptomatic hemodialysis patients aged ≥ 40 years, measured before and after dialysis within one month. Patients were followed for up to 12 months. Results: Fifty-six patients were enrolled. The mean hs-cTnI levels were 28.4 ng/L pre-dialysis and 27.9 ng/L post-dialysis, with ranges of <6–223 ng/L and <6–187 ng/L, respectively. The mean hs-cTnI delta between pre- and post-dialysis was −0.5 ng/L, with 52% showing a negative delta, 30% no change, and 18% a positive delta. No association was found between baseline hs-cTnI levels and mortality or hospitalization during follow-up. Conclusions: Most asymptomatic hemodialysis patients had hs-cTnI levels in the “gray zone”, thus neither confirming nor excluding acute myocardial infarction. Dialysis did not significantly affect hs-cTnI levels, and elevated baseline hs-cTnI was not linked to increased mortality or hospitalization over 12 months. Full article