Validation of an Inhaled Therapy Beliefs Questionnaire in Patients with Chronic Obstructive Pulmonary Disease.

Background: To carry out a validation questionnaire that assesses beliefs about inhaled treatments in patients with chronic obstructive pulmonary disease (COPD), as knowing patients' beliefs could help to improve medication adherence and health outcomes. Methods: We evaluated data from 260 COPD patients from electronic medical record databases from five primary healthcare centers, in a descriptive, cross-sectional study with a sample size calculated for a 10-item questionnaire, with an estimated Cronbach's alpha of 0.70 and a 95% confidence level. Study participants were selected via systematic random sampling. Variables: Ten-item Inhaled Therapy Beliefs Questionnaire, CCTI-Questionnaire v.2.0, time for completion, age, sex, educational level, spirometry severity (GOLD criteria), exacerbations (previous year), characteristics of inhaled treatment, and smoking habit. A two-year follow-up in a subsample of 77 patients from one health center was utilized. The Morisky-Green test, pharmacy dispensing data, test-retest (kappa coefficient), and an exploratory analysis of the adherence-belief relationship (ji-squared) were measured. Results: The 10-item questionnaire showed good viability (3 min completion time) when performed face-to-face or telephonically; its psychometric properties were acceptable, with an internal consistency (Cronbach's alpha) score of 0.613. Three factors explained 47.58% of the total variance (p < 0.0001): use (factor 1), effects (factor 2), and objectives (factor 3) of inhalers. The two-year follow-up ultimately considered 58 out of the 77 patients (10 deceased, 4 unlocated, 2 mistakes, 2 no inhaled treatment, and 1 withdrawal). Non-adherence was 48.3% in terms of the Morisky-Green test; 31% in terms of pharmacy dispensing data; and 40.4% considering both methods. There was low test-retest reliability, indicated by items 4, 8, and 9 of the CCTI-Questionnaire (Kappa = 0.4, 0.26, and 0.34; p-value < 0.0001, 0.008, and 0.001, respectively). There was mild correlation between beliefs and adherence. Conclusions: The ten-item CCTI-Questionnaire v.2.0 demonstrated acceptable psychometric properties regarding feasibility, reliability, and content validity.

Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.

Analysis of the circumstances associated with death and predictors of mortality in Spanish adults with Down syndrome, 1997-2014.

OBJECTIVES: Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality. PATIENTS AND METHODS: Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables. RESULTS: We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50-59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30-3.77]) or cancer (aOR 2.79 [2.07-3.75]), gross aspiration's admission (aOR 2.59 [2.20-3.04]), immobility (aOR 2.31 [1.46-3-62]), and readmission within 30 days (aOR 2.43 [2.06-2.86]) were identified as predictors of mortality. CONCLUSIONS: Adults with DS have a high in-hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia.

ELM-the Eukaryotic Linear Motif resource-2024 update.

Short Linear Motifs (SLiMs) are the smallest structural and functional components of modular eukaryotic proteins. They are also the most abundant, especially when considering post-translational modifications. As well as being found throughout the cell as part of regulatory processes, SLiMs are extensively mimicked by intracellular pathogens. At the heart of the Eukaryotic Linear Motif (ELM) Resource is a representative (not comprehensive) database. The ELM entries are created by a growing community of skilled annotators and provide an introduction to linear motif functionality for biomedical researchers. The 2024 ELM update includes 346 novel motif instances in areas ranging from innate immunity to both protein and RNA degradation systems. In total, 39 classes of newly annotated motifs have been added, and another 17 existing entries have been updated in the database. The 2024 ELM release now includes 356 motif classes incorporating 4283 individual motif instances manually curated from 4274 scientific publications and including >700 links to experimentally determined 3D structures. In a recent development, the InterPro protein module resource now also includes ELM data. ELM is available at: http://elm.eu.org.

Impact of peritoneal dialysis strategy on technique and patient survival.

Background: The aim of this study was to evaluate the impact of peritoneal dialysis (PD) strategy on technique and patient survival. Methods: This was a retrospective, single-center study conducted on consecutive patients with chronic kidney disease who underwent PD between January 2009 and December 2019. The study sample was stratified into four different groups according to PD technique [automated (APD) or manual (CAPD)] and icodextrin use (yes versus no). The primary endpoints were survival of both technique and patient. Results: A total of 531 patients were included in the analysis. Mean ± standard deviation age was 60.6 ± 14.6 years, 68.4% (363) were men and 34.8% (185) had diabetes. The median technique survival time was 19 (15) months. A total of 185 (34.8%), 96 (18.1%), 99 (18.7%) and 151 (28.4%) patients were included in the CAPD/No-Icodextrin, CAPD/Icodextrin, APD/No-Icodextrin and APD/Icodextrin study groups, respectively. Throughout the study, 180 (33.9%) patients underwent renal transplant, 71 (13.4%) were changed to hemodialysis and 151 (28.4%) died. Age [hazard ratio (HR) 0.975, 95% confidence interval (CI) 0.960-0.990, P = .001] and incidence of early peritoneal infection (HR 2.440, 95% CI 1.453-4.098, P = .001) were associated with technique survival, while age (HR 1.029, 95% CI 1.013-1.045, P < .001), Charlson Index (HR 1.192, 95% CI 1.097-1.295, P < 0.001), use of icodextrin (HR 0.421, 95% CI 0.247-0.710, P < .001) and APD/Icodextrin (HR 0.499, 95% CI 0.322-0.803, P = .005) were associated with patient survival. Conclusions: Icodextrin use and APD/Icodextrin had a positive impact on patient survival, while older age and higher Charlson Index had a negative one. Age and incidence of early peritoneal infection significantly impacted on technique survival.

Vascular protection with rivaroxaban in the comprehensive management of atrial fibrillation.

INTRODUCTION: In addition to an increased risk of thromboembolic complications, patients with atrial fibrillation (AF) are at risk for vascular events. Consequently, complete vascular protection is warranted in these patients. AREAS COVERED: A narrative search was conducted on PubMed (MEDLINE), using the MeSH terms [Rivaroxaban] + [Atrial fibrillation] + [Cardiovascular] + [Vascular] + [Treatment]. Original data from clinical trials, prospective and retrospective studies, useful reviews and experimental studies, were selected. EXPERT OPINION: The ROCKET-AF trial showed that rivaroxaban is effective in reducing the risk of stroke, with a lower risk of fatal and intracranial bleeding compared to warfarin. Remarkably, experimental data have provided a number of pathogenic mechanisms through which rivaroxaban could provide beneficial vascular properties beyond its antithrombotic activity. Moreover, in the AF population, additional to its ability to reduce the risk of thromboembolic complications, rivaroxaban is associated with a lower risk of myocardial infarction, major adverse cardiac and limb events, and vascular mortality in patients with diabetes, also attenuating renal impairment during follow-up. These findings suggest that rivaroxaban may provide a comprehensive vascular protection in patients with AF.

Should atrial fibrillation be considered a vascular disease? The need for a comprehensive vascular approach.

INTRODUCTION: Atrial fibrillation (AF) cannot be considered an isolated disease. Patients with AF should be managed using a comprehensive approach that is not limited to stroke prevention. AREAS COVERED: In this manuscript, the potential role of AF as a vascular disease that is managed as part of a holistic approach was reviewed. EXPERT OPINION: The residual risk of stroke in patients with AF reaches 1-2% annually, despite appropriate anticoagulation therapy. Additionally, patients with AF may develop cognitive impairment through stroke-independent pathways. Furthermore, patients with AF may have a higher risk of developing atherosclerotic vascular disease in various vascular beds and chronic kidney disease; conversely, patients with atherosclerotic disease may have an increased risk of developing AF. AF should be considered a truly systemic vascular disease, since it brings together several hemodynamic and systemic changes, including inflammation, oxidative stress, activation of the renin-angiotensin-aldosterone and sympathetic systems, as well as a prothrombotic state and endothelial dysfunction. In this regard, patients with AF should be treated based on a holistic approach that is not limited to oral anticoagulation but includes complete vascular protection.

Multivariate reference and tolerance regions based on conditional transformation models: Application to glycemic markers.

The reference interval is the most widely used medical decision-making, constituting a central tool in determining whether an individual is healthy or not. When the results of several continuous diagnostic tests are available for the same patient, their clinical interpretation is more reliable if a multivariate reference region (MVR) is available rather than multiple univariate reference intervals. MVRs, defined as regions containing 95% of the results of healthy subjects, extend the concept of the reference interval to the multivariate setting. However, they are rarely used in clinical practice owing to difficulties associated with their interpretability and the restrictions inherent to the assumption of a Gaussian distribution. Further statistical research is thus needed to make MVRs more applicable and easier for physicians to interpret. Since the joint distribution of diagnostic test results may well change with patient characteristics independent of disease status, MVRs adjusted for covariates are desirable. The present work introduces a novel formulation for MVRs based on multivariate conditional transformation models (MCTMs). Additionally, we take into account the estimation uncertainty of such MVRs by means of tolerance regions. These conditional MVRs imply no parametric restriction on the response, and potentially nonlinear continuous covariate effects can be estimated. MCTMs allow the estimation of the effects of covariates on the joint distribution of multivariate response variables and on these variables' marginal distributions, via the use of most likely transformation estimation. Our contributions proved reliable when tested with simulated data and for a real data application with two glycemic markers.

A cross-country study on the impact of governmental responses to the COVID-19 pandemic on perinatal mental health.

This study aimed to analyse the role of governmental responses to the coronavirus disease 2019 (COVID-19) outbreak, measured by the Containment and Health Index (CHI), on symptoms of anxiety and depression during pregnancy and postpartum, while considering the countries' Inequality-adjusted Human Development Index (IHDI) and individual factors such as age, gravidity, and exposure to COVID-19. A cross-sectional study using baseline data from the Riseup-PPD-COVID-19 observational prospective international study (ClinicalTrials.gov: NCT04595123) was carried out between June and October 2020 in 12 countries (Albania, Brazil, Bulgaria, Chile, Cyprus, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom). Participants were 7645 pregnant women or mothers in the postpartum period-with an infant aged up to 6 months-who completed the Edinburgh Postnatal Depression Scale (EPDS) or the Generalised Anxiety Disorder Assessment (GAD-7) during pregnancy or the postpartum period. The overall prevalence of clinically significant depression symptoms (EPDS ≥ 13) was 30%, ranging from 20,5% in Cyprus to 44,3% in Brazil. The prevalence of clinically significant anxiety symptoms (GAD-7 ≥ 10) was 23,6% (ranging from 14,2% in Israel and Turkey to 39,5% in Brazil). Higher symptoms of anxiety or depression were observed in multigravida exposed to COVID-19 or living in countries with a higher number of deaths due to COVID-19. Furthermore, multigravida from countries with lower IHDI or CHI had higher symptoms of anxiety and depression. Perinatal mental health is context-dependent, with women from more disadvantaged countries at higher risk for poor mental health. Implementing more restrictive measures seems to be a protective factor for mental health, at least in the initial phase of the COVID-19.

Mindfulness Prevents Depression and Psychopathology in Elderly People with Mild to Moderate Alzheimer's Disease: A Randomized Clinical Trial.

BACKGROUND: This longitudinal study addressed whether mindfulness practice prevents psychological and behavioral symptoms, especially mood disorders, in Alzheimer's disease (AD). OBJECTIVE: To assess the incidence of depression in the course of AD and to determine which non-pharmacological treatment (NPT) is most effective in preventing psychopathological symptoms. METHODS: We conducted a longitudinal, non-inferiority and equivalence randomized clinical trial, repeated-measures design, with a control group and three experimental treatments: mindfulness, cognitive stimulation, and relaxation. Each experimental group performed three weekly sessions for two years. The pharmacological treatment of all participants was donepezil (10 mg). Participants were patients with probable AD without diagnosed depression from the public neurology services of the Canary Health Service, Spain. Psychological evaluation was performed using the Geriatric Depression Scale (GDS), Hamilton Depression Rating Scale (HDRS), and Neuropsychiatric Inventory (NPI-Q). The statistical analysis included only patients who attended at least 75% of the sessions. A nonparametric, repeated-measures analysis was performed with Kruskal-Wallis H test and between-group differences with Mann-Whitney U test with Bonferroni correction (p < 0.008). Effect size was calculated with partial eta-squared. RESULTS: The results showed significant differences with large effect sizes (η2p>0.14) between mindfulness and the rest of the experimental groups as well as the control in the GDS, HDRS, and NPI-Q scales. CONCLUSION: Compared to the other experimental groups, only mindfulness prevented the onset of depression and other psychopathologies in early-stage AD. Based on its effectiveness in maintaining cognitive functions and preventing psychopathology, we recommend mindfulness as the first-choice NPT for mild to moderate AD.

What brings adults with Down syndrome to the hospital? A retrospective review of a Spanish cohort between 1997 and 2014.

OBJECTIVES: To describe the clinical and epidemiological characteristics of adult patients with Down syndrome admitted to Spanish hospitals between 1997 and 2014. Secondary goals were to study trend changes over time, and to analyse differences between patients admitted to medical and surgical departments. PATIENTS AND METHODS: Retrospective observational study on data collected from the Minimum Basic Dataset (MBDS, Conjunto Mínimo Básico de Datos [CMBD]) of admissions of adults with Down syndrome to hospitals belonging to the Spanish National Health System from 1 January 1997 through 31 December 2014. We analysed epidemiological and clinical variables. RESULTS: We analysed 28,716 admissions of 16,874 adult patients with Down syndrome. Men accounted for 58.2% of the sample, and the mean age on admission was 41 ± 13 years, with an 11-year increase in mean age during the study period. Admissions among persons with Down syndrome increased by 5% during the study period, with a noticeable rise in admissions of older adults and to medical departments. Almost one-third of patients (31.8%) were admitted more than once. Age-adjusted mortality was 15.7%. The most common comorbid conditions were chronic obstructive pulmonary disease (25%), hypothyroidism (18.6%), and epilepsy (14.3%). The departments with the highest numbers of admissions were internal medicine (26.3%), pulmonary medicine (6.9%), and general surgery (5.25%). CONCLUSION: Hospital admissions among Spanish adults with Down syndrome have increased in recent decades, especially in older patients. We identified substantial differences between patients admitted to medical and surgical departments.

Segmentation of Medical Image Using Novel Dilated Ghost Deep Learning Model.

Image segmentation and computer vision are becoming more important in computer-aided design. A computer algorithm extracts image borders, colours, and textures. It also depletes resources. Technical knowledge is required to extract information about distinctive features. There is currently no medical picture segmentation or recognition software available. The proposed model has 13 layers and uses dilated convolution and max-pooling to extract small features. Ghost model deletes the duplicated features, makes the process easier, and reduces the complexity. The Convolution Neural Network (CNN) generates a feature vector map and improves the accuracy of area or bounding box proposals. Restructuring is required for healing. As a result, convolutional neural networks segment medical images. It is possible to acquire the beginning region of a segmented medical image. The proposed model gives better results as compared to the traditional models, it gives an accuracy of 96.05, Precision 98.2, and recall 95.78. The first findings are improved by thickening and categorising the image's pixels. Morphological techniques may be used to segment medical images. Experiments demonstrate that the recommended segmentation strategy is effective. This study rethinks medical image segmentation methods.

Clinical Profile and Management of Patient Patients with Ischemic Heart Disease and/or Peripheral Artery Disease in Clinical Practice: The APALUSA Study.

This study was aimed to ascertain the clinical profile and management of patients with ischemic heart disease (IHD) and/or peripheral artery disease (PAD). In this observational and cross-sectional study developed in 80 hospitals throughout Spain, consecutive adults with stable IHD and/or PAD were included. A total of 1089 patients were analyzed, of whom 65.3% had only IHD, 17.8% PAD and 16.9% both. A total of 80.6% were taking only one antiplatelet agent, and 18.2% were on dual antiplatelet therapy (mainly aspirin/clopidogrel). Almost all patients were taking ≥1 lipid lowering drug, mainly moderate-to-high intensity statins. IHD patients took ezetimibe more commonly than PAD (43.9% vs. 12.9%; p < 0.001). There were more patients with IHD that achieved blood pressure targets compared to PAD (<140/90 mmHg: 67.9% vs. 43.0%; p < 0.001; <130/80 mmHg: 34.1% vs. 15.7%; p < 0.001), LDL-cholesterol (<70 mg/dL: 53.1% vs. 41.5%; p = 0.033; <55 mg/dL: 26.5% vs. 16.0%; p = 0.025), and diabetes (HbA1c < 7%, with SGLT2i/GLP1-RA: 21.7% vs. 8.8%; p = 0.032). Modifications of antihypertensive agents and lipid-lowering therapy were performed in 69.0% and 82.3% of patients, respectively, without significant differences between groups. The use of SGLT2i/GLP1-RA was low. In conclusion, cardiovascular risk factors control remains poor among patients with IHD, PAD, or both. A higher use of combined therapy is warranted.

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial.

Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020).

Longitudinal relationship of liver injury with inflammation biomarkers in COVID-19 hospitalized patients using a joint modeling approach.

The mechanisms underlying liver disease in patients with COVID-19 are not entirely known. The aim is to investigate, by means of novel statistical techniques, the changes over time in the relationship between inflammation markers and liver damage markers in relation to survival in COVID-19. The study included 221 consecutive patients admitted to the hospital during the first COVID-19 wave in Spain. Generalized additive mixed models were used to investigate the influence of time and inflammation markers on liver damage markers in relation to survival. Joint modeling regression was used to evaluate the temporal correlations between inflammation markers (serum C-reactive protein [CRP], interleukin-6, plasma D-dimer, and blood lymphocyte count) and liver damage markers, after adjusting for age, sex, and therapy. The patients who died showed a significant elevation in serum aspartate transaminase (AST) and alkaline phosphatase levels over time. Conversely, a decrease in serum AST levels was observed in the survivors, who showed a negative correlation between inflammation markers and liver damage markers (CRP with serum AST, alanine transaminase [ALT], and gamma-glutamyl transferase [GGT]; and D-dimer with AST and ALT) after a week of hospitalization. Conversely, most correlations were positive in the patients who died, except lymphocyte count, which was negatively correlated with AST, GGT, and alkaline phosphatase. These correlations were attenuated with age. The patients who died during COVID-19 infection displayed a significant elevation of liver damage markers, which is correlated with inflammation markers over time. These results are consistent with the role of systemic inflammation in liver damage during COVID-19.